ACS Publications. Most Trusted. Most Cited. Most Read
Quick View

OR SEARCH CITATIONS

My Activity
Publications
CONTENT TYPES

Figure 1Loading Img
Download Hi-Res ImageDownload to MS-PowerPointCite This:ACS Nano 2020, 14, 10, 12522-12537
RETURN TO ISSUEPREVReviewNEXT

COVID-19 Vaccine Frontrunners and Their Nanotechnology Design

  • Young Hun Chung
    Young Hun Chung
    Department of Bioengineering, University of California San Diego, La Jolla, California 92093, United States
    More by Young Hun Chung
    Orcidhttp://orcid.org/0000-0002-6578-8076
  • , 
  • Veronique Beiss
    Veronique Beiss
    Department of NanoEngineering, University of California San Diego, La Jolla, California 92093, United States
    More by Veronique Beiss
  • , 
  • Steven N. Fiering*
    Steven N. Fiering
    Geisel School of Medicine, Dartmouth College, Hanover, New Hampshire 03755, United States
    Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire 03766, United States
    *Email: [email protected]
    More by Steven N. Fiering
  • , and 
  • Nicole F. Steinmetz*
    Nicole F. Steinmetz
    Department of Bioengineering, University of California San Diego, La Jolla, California 92093, United States
    Department of NanoEngineering, University of California San Diego, La Jolla, California 92093, United States
    Department of Radiology, University of California San Diego, La Jolla, California 92093, United States
    Moores Cancer Center, University of California San Diego, La Jolla, California 92093, United States
    Center for Nano-ImmunoEngineering, University of California San Diego, La Jolla, California 92093, United States
    *Email: [email protected]
    More by Nicole F. Steinmetz
    Orcidhttp://orcid.org/0000-0002-0130-0481
Cite this: ACS Nano 2020, 14, 10, 12522–12537
Publication Date (Web):October 9, 2020
https://doi.org/10.1021/acsnano.0c07197
Copyright © 2020 American Chemical Society
Request reuse permissions
  • Open Access

Article Views

62295

Altmetric

-

Citations

247
LEARN ABOUT THESE METRICS
PDF (3 MB)
Get e-Alerts
Supporting Info (1)»
SUBJECTS:

Abstract

High Resolution Image
Download MS PowerPoint Slide

Humanity is experiencing a catastrophic pandemic. SARS-CoV-2 has spread globally to cause significant morbidity and mortality, and there still remain unknowns about the biology and pathology of the virus. Even with testing, tracing, and social distancing, many countries are struggling to contain SARS-CoV-2. COVID-19 will only be suppressible when herd immunity develops, either because of an effective vaccine or if the population has been infected and is resistant to reinfection. There is virtually no chance of a return to pre-COVID-19 societal behavior until there is an effective vaccine. Concerted efforts by physicians, academic laboratories, and companies around the world have improved detection and treatment and made promising early steps, developing many vaccine candidates at a pace that has been unmatched for prior diseases. As of August 11, 2020, 28 of these companies have advanced into clinical trials with Moderna, CanSino, the University of Oxford, BioNTech, Sinovac, Sinopharm, Anhui Zhifei Longcom, Inovio, Novavax, Vaxine, Zydus Cadila, Institute of Medical Biology, and the Gamaleya Research Institute having moved beyond their initial safety and immunogenicity studies. This review analyzes these frontrunners in the vaccine development space and delves into their posted results while highlighting the role of the nanotechnologies applied by all the vaccine developers.

KEYWORDS:

  Note

This article is made available via the ACS COVID-19 subset for unrestricted RESEARCH re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

Background

ARTICLE SECTIONS
Jump To
In December 2019, the World Health Organization (WHO) Country Office in China was first alerted to an unknown outbreak of contagious and often severe lower respiratory illnesses originating from the city of Wuhan, the biggest city in and capital of China’s Hubei province. (1) The cause of the respiratory illness is a virus of the betacoronavirus class now termed coronavirus infectious disease-19 (COVID-19). The virus was named SARS-CoV-2 due to its genetic and structural similarity with SARS-CoV. (1,2) On March 11, 2020, the WHO officially identified SARS-CoV-2 as a pandemic due to its quick global spread. (1) As of August 11, 2020, there are 19,936,210 confirmed cases worldwide and 732,499 deaths due to SARS-CoV-2. (3) The continued rise of both cases and deaths necessitates the rapid development of an effective SARS-CoV-2 vaccine. The second wave happening in some countries that have reopened their economies further accentuates this need. (4,5) While masking, social distancing, and contact tracing can slow the spread of this virus, it appears too infectious to be eliminated by these strategies, and a vaccine is essential to enable a return to normal human social interaction.
Fortunately, in the relatively few months since SARS CoV-2 was identified as the cause of COVID-19, over two hundred academic laboratories and companies have undertaken vaccine development, and many are making record time in advancing to clinical trials (Table S1). (6,7) Moderna reached clinical trials 63 days after their sequence selection. (8) It is striking that an unestablished nanotechnology formulation reached clinical testing almost a full month before established approaches (i.e., inactivated and live-attenuated vaccines) entered clinical trials. (9,10) This highlights the opportunity for less developed technology platforms in vaccine development and, if proven successful, may enable a more rapid response to future emergent infectious diseases. It is also of note that in previous severe coronavirus outbreaks of SARS-CoV and MERS-CoV clinical trials were not reached until 25 and 22 months after the outbreaks began. (11) Older severe infectious disease outbreaks such as Dengue and Chikungunya did not reach clinical trials until 52 and 19 years after the outbreak. (11) The improved speed into clinical trials is hopeful, but despite the rapid progress, there are still reasons for concern.
Vaccine development takes time as the vaccines must not only be protective but also safe. Unlike other drugs that are delivered into sick patients, vaccines are administered into healthy patients and require very high safety margins. (12) Therefore, the population should be carefully monitored if vaccine candidates are widely administered based on Emergency Use Authorization. This is especially vital as for past respiratory diseases such as SARS-CoV, MERS-CoV, respiratory syncytial virus, and measles it had been shown that antibodies can exacerbate disease severity through antibody-dependent enhancement. (13) Many of the vaccines that are frontrunners are preclinical nanotechnologies and have not been proven in clinical settings. For instance, mRNA vaccines have been in development and clinical testing for the past 30 years, but the technology has not been previously approved. (14) The platform technology offers speed and adaptability, so these vaccine candidates can be rapidly developed by repurposing previously developed nanostructures as shown by Moderna. (15) Likewise, Novavax’s vaccine is also modeled off of their previous vaccine against influenza. (16) Even so, the vaccines must be rigorously tested for safety before widespread vaccination can occur, which Moderna and Novavax have accomplished through their Phase I studies. (17,18) Beyond Moderna and Novavax, several other companies have moved beyond their safety and immunogenicity Phase I and II clinical studies and have released pertinent data corresponding to these trials. (17,19−23) This review analyzes these posted results and highlights the nanotechnological aspects of the vaccines from these leading companies as well as summarizes the potential of other rapidly developed vaccines in clinical trials.

Vaccination Immunology

ARTICLE SECTIONS
Jump To
To gain a better understanding of the clinical data, it is important to understand concepts in vaccine immunology. There is no “one size fits all” protective antiviral immune response. Every virus is different with different routes of infection, different range of infectable cell types, and different associated pathology. Accordingly, the immune response best suited for protection against each virus will also be variable. (24) Other factors such as sex, age, pregnancy, and route of infection can also influence the immune response. (24,25) It is widely reported that some people become heavily infected with SARS-CoV-2, but remain asymptomatic, and that some become critically ill and succumb to the disease. This extreme variability in response to infection underscores the variability of individual immune responses to this virus, suggesting that there may not be a single perfect strategy that will achieve uniform long-lasting immunity in everyone. The specific immune responses that elicit the most rapid and dependable viral clearance need to be understood and replicated by the vaccines. Major unanswered questions are whether humoral and/or cellular cytotoxic responses are required, what types of helper T cells are most effective (e.g., Th1 vs Th2 vs Th17) as well as what isotype of antibody response (e.g. IgG vs IgA) most effectively protects against this virus. (26−28) Most of these questions are being answered through laboratory studies as well as through analysis of serum and circulating cells from recovered patients.
Given the variability of host immune responses, there is unfortunately no guarantee that a vaccine, even if it has progressed into advanced clinical trials, will protect against SARS-CoV-2. While a single vaccination can confer lifelong protection against small pox (29) or poliovirus, (30) HIV continues to evade protection by vaccination despite a major worldwide effort to develop an effective HIV vaccine. (31) Additionally, there are indications that respiratory viruses are especially difficult to protect against with vaccines. The respiratory syncytial virus is a prime example in which there are no approved vaccines, despite considerable efforts to develop one. (32)
One reason for vaccine failure against respiratory viruses is that the respiratory tract, including the lungs, is an external mucosal surface that is protected by the generation of secreted IgA antibodies; yet, the antibodies measured to determine whether an experimental subject has “responded” to a vaccine often focus on IgG, IgM, or total immunoglobulin in the blood. (33,34) Most vaccines are delivered intramuscularly, and mucosal immunity and IgA secretion is thereby minimal. (35) Furthermore, eliciting IgA production from conventional vaccines is difficult, and vaccines may lack the immunogenicity required to elicit necessary IgA protection. (36) Regardless, there are efforts and reports on development of SARS-CoV-2 vaccine candidates that can elicit IgA responses (see Table S1). For instance, Altimmune, an adenovirus (Ad)-based nonreplicating viral vector vaccine administered intranasally, showed 29-fold IgA induction in mice. (37) Other companies such as Stabilitech Biopharma Limited and Quadram Institute Biosciences are also developing mucosal vaccines. (38,39) The value of IgA or other immunoglobulin isotypes in protection against SARS-CoV-2 has not been fully elucidated, but it is believed that IgA can prevent SARS-CoV-2 binding to the airway epithelium thereby helping to block both initial infection and subsequent transmission. (34,37) It is important to note that it is not known what role, if any, IgA plays in protection against SARS-CoV-2 and that many of the current vaccines are not specifically looking to activate IgA responses. Of course, it is possible that IgA production will not be important for an effective vaccine, or may even be harmful, as IgA production was negatively correlated to increased severity in COVID-19 patients. (40)
SARS-CoV-2 is unusual for a respiratory virus in that it binds to a receptor, angiotensin converting enzyme 2 (ACE2), expressed in virtually all organs, (40) but especially in the lungs, (41) brain, (42) and gut. (43) Therefore, unlike most respiratory viruses, SARS-CoV-2 has broader biodistribution and can cause considerable damage outside the respiratory system. It adversely affects the digestive, urogenital, central nervous, and circulatory systems, and the pervasiveness of the ACE2 receptor is why symptoms are highly variable and can range among dyspnea, diarrhea, headache, high blood pressure, venous thromboembolism, and more. (40) Therefore, since much of the pathology is outside the airway due to systemic viral infection, a vaccine that elicits IgG antibodies could protect patients from systemic circulation of the virus. IgG antibodies opsonize the targeted antigens presenting the opsonized products to phagocytes while also activating the complement system. (44)
Another hallmark of vaccine development is T-cell involvement, and differences in T-cell responses can influence generation of high affinity and neutralizing antibodies (NAbs) as well as elimination of infected cells. (45) Immune memory and generation of high affinity class-switched antibodies are highly dependent on T-cells and normally do not develop without proper T-cell involvement. (46,47) Immune memory is the main driver of long-term immunoprotection, and studies have shown that immune titers from patients infected with the first SARS-CoV can have significant antibody levels for up to 3 years postinfection. (48) Such antibody maintenance would be extremely beneficial in the fight against SARS-CoV-2, and this prolonged immune memory could potentially confer long-term protection by a vaccine. However, it is likely that periodic booster vaccination will be necessary in areas of rebounding cases as is done for other infectious diseases.
It is currently unclear whether any of the tested vaccines will confer protection against SARS-CoV-2. Fortunately, as noted below, there are encouraging early results from multiple vaccines that are safe and immunogenic in limited patients. This early success warrants the progression into Phase III clinical trials, and expectations are that 20,000–40,000 subjects would be involved. There is a daunting task left in the effort to develop effective vaccine(s) against SARS-CoV-2, and no guarantee of success, but we are encouraged by the early testing success and rapid development of so many candidate vaccines.

Nanotechnology Offers Opportunities in Vaccine Design

ARTICLE SECTIONS
Jump To
Nanoparticles and viruses operate at the same size scale; therefore, nanoparticles have an ability to enter cells to enable expression of antigens from delivered nucleic acids (mRNA and DNA vaccines) and/or directly target immune cells for delivery of antigens (subunit vaccines). Many vaccine technologies employ these direct benefits by encapsulating genomic material or protein/peptide antigens in nanoparticles such as lipid nanoparticles (LNPs) or other viruses such as Ads. BioNTech/Pfizer and Moderna encapsulate their mRNA vaccines within LNPs while the University of Oxford/Astrazeneca (from here on out referred to as Oxford/Astrazeneca) and CanSino incorporate antigen-encoding sequences within the DNA carried by Ads. (17,19,22,23) Novavax decorates recombinant S proteins of SARS-CoV-2 onto their proprietary virus like particle (VLP) nanoparticles. (49) The nanoparticles are described in further detail in the discussion below.
Beyond antigen delivery, nanoparticles can codeliver adjuvants to help prime the desired immune responses. Adjuvants are immunostimulatory molecules administered together with the vaccine to help boost immune responses mainly by activating additional molecular receptors that predominantly recognize pathogens or danger signals. These pathways function primarily within the innate immune system, and each adjuvant generally has a different range of stimulation of these pathogen or danger receptors. While the vaccine goal is to stimulate recognition and response by lymphocytes, not innate cells, the activation of the innate immune cells is required to activate the lymphocytes to obtain both B and T-cell responses. (50,51) Encapsulation and/or conjugation of both the adjuvant and antigen within the same nanoparticle enables targeted, synchronous delivery to the same antigen presenting cell (APC). Many adjuvants have previously failed in the clinic due to toxicity issues, and this codelivery can help to direct antigen and adjuvant activity only in APCs that have taken up the antigen thereby reducing off-target side effects. (52) Targeted delivery of appropriate adjuvants can also reduce the necessary antigen dose for immune protection thereby producing a dose-sparing effect. (52) This effect would be abundantly helpful practically and financially in the current pandemic due to the enormous number of doses needed for global vaccination. Furthermore, when adjuvants and antigens are not codelivered they may dissociate quickly within the body, which may lead to off-target effects and/or rapid degradation of the adjuvant reducing the potency of the vaccine. (53) Both Moderna and BioNTech encapsulate their mRNA vaccines within LNPs to protect the mRNA from nuclease degradation. (17,19) Loss of temporal synchronization, i.e., uptake of the antigen and adjuvant by APCs at separate times, can also lead to autoimmunity against host proteins, as the adjuvant can activate APCs that are not primed against the antigen but rather primed against self-antigens. (52) Therefore, nanotechnology offers an opportunity in vaccine design, and there are several strategies that enable codelivery of SARS-CoV-2 antigens and adjuvants. The three main methods are (i) codelivery through encapsulation within or conjugation onto a nanoparticle, (ii) direct antigen-adjuvant conjugation, and (iii) utilizing the delivery vehicle as an adjuvant. (53,54) Another benefit that nanoparticles can confer is multivalent antigen presentation and orientation of subunit antigens in their native form. (55) For example, BioNTech/Pfizer, one of the frontrunner companies producing a SARS-CoV-2 vaccine, formulates their receptor binding domain (RBD) antigens onto a T4 fibritin-derived “foldon” trimerization base to better resemble the trimeric form of the spike (S) protein of SARS-CoV-2. (19,56) Furthermore, display of different RBD epitopes of influenza A on multivalent ferritin nanoparticles can increase production of cross-reactive B-cells against influenza A, and produce a more diverse and effective antibody response than ferritin nanoparticles with homotypic RBD display. (57) The study also found that the multivalent, heterotypic nanoparticles induced a broadly NAb response, which makes the generation of an all-encompassing, universal influenza A vaccine possible.
Lastly, due to the “nano” scale of nanomaterials as well as their composition, they can traffic in vivo differently from other materials. The lymphatic system is critical in initiating immune responses as APCs, and other lymphocytes travel from peripheral organs to nearby lymph nodes using the lymphatic system. (58) Accessing the lymphatic system can be challenging, but nanomaterials can traverse the interstitial spaces and access nearby lymph nodes. For instance, inhaled radiolabeled solid lipid nanoparticles were shown to traffic from the alveoli into nearby lymph nodes via the lymphatic system, while the free radiotracers trafficked via the systemic circulation. (59) Lymphatic drainage especially into lymph nodes near the lungs could be extremely beneficial in the fight against respiratory diseases such as SARS-CoV-2. Companies such as etheRNA and Intravacc are developing intranasally delivered vaccines delivered into the respiratory system that may target such nearby lymph nodes. (60,61)
For further reading on the opportunities of nanotechnology in SARS-CoV-2 vaccine design, we would like to refer the reader to the following review. (62) This review also discusses challenges and opportunities of the manufacturing processes and delivery platforms that are necessary for global vaccination.

The Landscape of COVID-19 Vaccine Candidates

ARTICLE SECTIONS
Jump To
According to the WHO and the Milken Institute, as of August 11, 2020, there are 202 companies and universities worldwide working on a coronavirus vaccine (Table S1). (7,63) The vaccine types vary from well-established vaccines (e.g., inactivated and live-attenuated) to vaccines that have recently gained clinical approval (e.g., subunit) to those that have not yet made the transition into the clinic (e.g., mRNA, DNA, nonreplicating viral vector, replicating viral vector) (Figure 1). Inactivated vaccines are similar to the native pathogen but are replication deficient due to chemical or heat treatment. (64) Live-attenuated vaccines are weakened forms of the virus that can replicate in a limited manner unable to cause the actual disease, (65) and subunit vaccines confer immunoprotection using portions of the virus. (66) Subunit vaccines are usually less immunogenic and require an adjuvant to stimulate the immune recognition of the antigens in the vaccine. Nucleic acid based vaccines can be mRNA or DNA based, and rather than directly injecting the antigen, express it within host cells using the genomic material. (67) Lastly, viral vector vaccines contain engineered genomes to encode the antigen of the target pathogen. When administered in vivo, the viral vectors enter target cells and the genomic material is transcribed and translated for in vivo antigen production. (68) They can, but do not always, possess the ability to replicate within the host. Replication deficient vaccines may impart better safety, but immune memory is not as long-lasting. Currently, there are no viral vector vaccines used in the clinic for humans, but there are some that have been utilized for veterinary applications. (69) Of the 202 companies, only a select few have advanced into clinical trials; as of August 11, 2020, the WHO indicates there are 29 vaccine candidates in clinical trials (Figure 2a,b). (7)Of these select few vaccines, even fewer have released data of their initial safety and immunogenicity from completed Phase I and II studies (Table 1). It is noteworthy that every company that has released data has reported positive results from their early Phase clinical trials, allowing advancement into wider and more broadly encompassing efficacy studies.

Figure 1

Figure 1. Vaccine types currently under development for SARS-CoV-2. (a) Inactivated vaccine that uses the native virus rendered replication deficient from heat or chemical treatment, (b) live-attenuated vaccine that can replicate, but in a limited manner that cannot cause the disease, (c) subunit vaccine that incorporates subsections of the native virus such as the S protein, (d) viral vector vaccine that encapsulates the genome of a different weakly pathogenic virus with additional DNA that encodes the target viral antigen, (e) DNA vaccine using a DNA plasmid that encodes the target antigen, often administered by electroporation, (f) RNA vaccine of RNA encapsulated within a LNP to decrease RNA degradation and increase translation efficiency. Graphics created with Biorender.com.

High Resolution Image
Download MS PowerPoint Slide

Figure 2

Figure 2. Graphs detailing the vaccines currently in development for SARS-CoV-2 according to the WHO and the Milken Institute as of August 11, 2020. (a) Pie chart of the vaccines by type, (b) bar graph showing the number of vaccines using adjuvants, (c) bar graph of the vaccine candidates in clinical trials.

High Resolution Image
Download MS PowerPoint Slide
Table 1. Summaries of Clinical Trials That Have Been Completed by Companies in the Vaccination Effort Against SARS-CoV-2a
a

Legend: blue = publicly released data from journals, green = unpublished publicly announced data, N/A = no answer, company did not report.

In this review, we discuss the vaccine nanotechnologies employed by the companies that have released their results in publication form. Two of the companies that have released early results are Moderna and the BioNTech/Pfizer partnership. While Moderna has already published their data in the New England Journal of Medicine, BioNTech/Pfizer’s data is currently prepublished in medRxiv and is awaiting peer review. (17,19) Both employ similar techniques for their vaccine, utilizing mRNA that encodes for subunits of the SARS-CoV-2 S protein (Table 2). On the other hand, Oxford/Astrazeneca and CanSino are both developing vaccines based on nonreplicating viral vectors. (7,22,23)
Table 2. Descriptions of Vaccines That Have Moved Beyond Their Initial Safety and Immunogenicity Phase I Studiesa
a

Legend: blue = publicly released data from journals, green = unpublished publicly announced data, N/A = no answer, company did not report.

In the clinic, both viral vector vaccines and mRNA vaccines have enjoyed variable successes with neither vaccine type currently approved for a specific use. mRNA vaccines and viral vector vaccines both depend on nucleic acids that encode the target antigen(s) but differ in their approach to vaccination. Instead of mRNA, viral vectors use DNA to encode the antigen of interest. Viral vector vaccines can impart high gene transduction capabilities due to their ability to enter into cells using the virus’ own receptor for infection, and efficient intracellular trafficking enables high production of target gene expression. (70) However, immunogenicity of the viral vectors and other adverse effects bear hurdles to safe use. The immunogenicity of the viral vector may decrease vaccine efficiency caused by NAbs against the viral vector in patients that either are developed during the course of vaccination or are pre-existing due to previous exposure to the Ad vectors they use. (70) Viral vectors that humans are not commonly exposed to such as the chimpanzee Ad utilized by Oxford/Pfizer can reduce neutralization. (23) Another safety concern for viral vectors is possible host genome integration, which may cause cancer if integrated into oncogenes and other regulatory sequences. (70)
mRNA vaccines are generally encapsulated within nanoparticles. Both BioNTech/Pfizer and Moderna encapsulate their RNA vaccines within LNPs, which may enable cytoplasmic delivery via fusogenic mechanisms. (17,19) However, neither Moderna nor BioNTech/Pfizer specifically mention the use of fusogenic LNPs although BioNTech/Pfizer does mention using cationic lipids. (71) Cytoplasmic delivery may improve translation efficiency, but it may also decrease RNA immunostimulation. RNA stimulates the immune system, and therefore acts as an adjuvant, by activating specific toll like receptors (TLRs), mainly TLRs 3, 7, and 8, which are all located within the cell’s endosomes. (72) TLRs 7 and 8 are especially important for mRNA vaccines as they recognize single stranded RNA and engage in virus recognition. (73) Encapsulation within nanoparticles improves RNA phagocytosis by APCs with subsequent localization within the endosomes. Failure of the RNA to be endocytosed can lead to nuclease degradation and weak immune stimulation. While advances in nanoparticle design have enabled cytoplasmic delivery of mRNA, synthetic nanoparticles do not match the efficiency of the machinery evolved by the viral vectors that enables trafficking inside the cell. Once inside the cell, the mRNA is translated directly within the cytoplasm; in contrast, DNA plasmids from the viral vectors need to be translocated into the nucleus, transcribed, and exported back to the cytoplasm. (74) This means that mRNA vaccines may produce greater amounts of antigen from smaller doses, but a caveat is that DNA tends to be more stable than mRNA meaning mRNA expression is generally shorter lived. The interplay between stability and translation efficiency can be a big determinant in effective antigen production. ()

Results–mRNA Vaccines: Moderna and BioNTech/Pfizer

ARTICLE SECTIONS
Jump To
As mentioned above, Moderna and BioNTech/Pfizer utilize mRNA vaccines that encode for the S protein of SARS-CoV-2. The S protein is the viral protein that binds to ACE2 on cells to mediate infection and is a frequent vaccine target since it is expected that antibodies binding to the correct epitope on the S protein could be neutralizing and therefore block intercellular viral spread. (2) The S protein has two subsections: S1 and S2. The S1 subunit contains the RBD and is responsible for initial attachment to the host cell through the ACE2 receptor, while the S2 subunit promotes viral fusion with cells to initiate infection. (2) Moderna’s vaccine, mRNA-1273, was codeveloped with the National Institute of Allergy and Infectious Diseases and specifically encodes the prefusion form of the S antigen (named S-2P) that includes a transmembrane anchor and an intact S1–S2 cleavage site. (17) Two proline substitutions in the vaccine mRNA at amino acids 986 and 987, which are within the central helix of the S2 subunit, keep the protein stable in its prefusion conformation. (56) The mRNA is encapsulated within an LNP composed of four lipids (Table 2). The exact formulation is not provided; however, inferences can be made based on previous LNP vaccines by Moderna, which utilize formulations of ionizable lipid, 1,2-distearoyl-sn-glycero-3-phosphocholine, cholesterol, and polyethylene glycol-lipid. (100) The exact lipids used are not stated. The mRNA-containing LNPs are solubilized and injected directly into the deltoid muscle. Moderna does not explicitly state the use of an adjuvant, but the LNP carrier may be an adjuvant since other lipids have been reported to have adjuvant properties (see the Discussion). (101)
The mRNA utilized by BioNTech/Pfizer encodes for the RBD. (19) Named BNT162b1, the mRNA is modified with single nucleoside incorporations of 1-methylpseudouridine (Table 2), which not only reduces the immunogenicity of the mRNA in vivo but also increases its translation. (102) The exact mechanism for increased translation has not been entirely elucidated, but one hypothesis is that the nucleoside modification improves RNA stability by decreasing rates of hydrolysis by phosphodiesterases. (103) Another study proved that RNA modification improves RNA secondary structure stability due to increased RNA stacking. (104) Additionally, as mentioned above, the formulated RBD antigen is constructed on a T4 fibritin-derived “foldon” trimerization base, which helps to guide antigen folding into the native trimeric state. (56,105) The T4 trimerization also augments the immunogenicity mainly due to the multivalent display offered in the trimerized state. (19) It is important to note that BioNTech/Pfizer is testing at least four mRNA vaccines in parallel (BNT162a1, BNT162b1, BNT162b2, and BNT162c2) although the prepublished manuscript only contains data from the BNT162b1 candidate. (77) Similar to Moderna, BioNTech/Pfizer has also encapsulated the mRNA within an LNP and administers the vaccine via intramuscular injection. (76) The LNP is provided from a partnership with Acuitas Therapeutics. The exact formulation is not specified, but previous publications from Acuitas Therapeutics states that their LNPs are formulated using ionizable cationic lipids, phosphatidylcholine, cholesterol, and polyethylene glycol-lipid with a ratio of 0.05 of RNA to lipid (w/w). Similarly to Moderna, the exact lipids used were not stated. (71) There is no indication that BioNTech/Pfizer utilizes an additional adjuvant with their vaccine although they do mention that the RNA acts as an adjuvant.
Both BioNTech/Pfizer and Moderna released encouraging safety and immunogenicity data. (17,19) Moderna tested a higher range of mRNA (25, 100, and 250 μg), while BioNTech/Pfizer tested 10, 30, and 100 μg. Safety evaluations noted no severe adverse events that warranted the discontinuation of either trial. Some of the more prominent adverse events in the Moderna trial included pain, headache, and chills, while BioNTech/Pfizer’s vaccine mainly caused pain, fatigue, and headache (Table 1). Antibody response was also positive in both trials. Moderna tested antibody response through ELISA assays while BioNTech/Pfizer utilized a RBD-binding IgG assay. (17,19) For Moderna, when comparing the response in vaccinated patients to convalescent serum from past SARS-CoV-2 patients, the 250 μg group generated higher S-2P geometric mean titers (GMTs) by day 15 (163,449 vs 142,140 arbitrary units (AU)), while the 25 and 100 μg groups produced higher GMTs by day 36 (391,018 and 781,399 AU, respectively), 7 days after a second boost. BioNTech/Pfizer recorded neutralizing anti-RBD titers much higher than convalescent serum levels. By day 21 (day of the second dose, or 21 days), the 30 μg group had a higher geometric mean concentration (GMC) than convalescent sera (1,536 vs 602 U/mL), while it took until day 28 (7 days after a second dose) for the 10 μg group (4,813 U/mL). The 100 μg group, which only used one dose, had higher GMC levels by day 21 (1,778 U/mL). Both Moderna and BioNTech/Pfizer tested T-cell responses and demonstrated TH1 skewed T-cell responses with detectable CD4+ and CD8+ response to their respective antigens. (17,20) Neither developer mentioned the production of antibodies other than IgG. It is difficult to directly compare the results between the trials because measurements and data reporting are not standardized, highlighting an opportunity and need to standardize vaccine trials and reporting requirements.
The vaccination schedule in the Phase III trials by both Moderna and BioNTech/Pfizer will not deviate from their Phase II setups. (106,107) Moderna will continue to boost on day 29 after an initial injection, and BioNTech/Pfizer will boost at day 21. However, Phase III trials will only evaluate one dose. In Moderna’s case, the midlevel dose led to higher immunogenicity than the highest dose while BioNTech/Pfizer demonstrated no substantial differences between their mid- and high-level doses. (17,19) Therefore, Moderna and BioNTech/Pfizer both chose to move forward with their midlevel doses (100 μg and 30 μg, respectively). For phase III, Moderna and BioNTech/Pfizer will also vaccinate much larger populations of 30,000 participants each. (108109110)

Results-Nonreplicating Viral Vector Vaccines: Oxford/Astrazeneca and CanSino

ARTICLE SECTIONS
Jump To
One of the most explored viral vector options is the Ad, which is currently being used by both CanSino and Oxford/Astrazenca (Table 2). Ads are common cold causing viruses that have a double-stranded DNA genome. Specifically, CanSino is utilizing Ad type 5 (Ad5), giving the vaccine the name Ad5-nCoV. (21) Oxford/Astrazeneca is employing a different viral vector, an Ad derived from the chimpanzee (the use of the chimpanzee vector minimizes possible interaction with prevalent antibodies against Ads), which was subsequently named AZD1222. (23) Ad5-nCoV specifically encodes for the full-length S protein of SARS-CoV-2, unlike both Moderna and BioNTech/Pfizer, which both encoded subunits of the S protein. The gene was derived from the Wuhan-Hu-1 sequence for SARS-CoV-2 and, along with a tissue plasminogen activator signal peptide, was cloned into an E1 and E3 deleted Ad5 vector. (21) Deletion of E1 inactivates the replication potential of the vaccine while deletion of E3 allows for the insertion of larger genes up to 8 kb. (113) The CanSino vectors were solubilized and administered intramuscularly into the arms of patients. Each shot contained 5 × 1010 viral particles per dose, and patients being tested with higher doses would receive multiple shots allowing for administration of multiples of 5 × 1010 particles.
AZD1222 is designed similarly to Ad5-nCoV, with deletion of E1 to block replication and deletion of E3 to enable incorporation of larger genetic cargo into the viral vector. (23,113) The added sequence encodes for the full-length S protein with a tissue plasminogen activator leader sequence, and the S protein sequence is codon-optimized. Key differences between the two viral vector platforms is discussed in more detail within the discussion section. Neither vaccine manufacturer mentions the use of an adjuvant, so these vectors most likely depend on immune recognition of the nonreplicating virus, perhaps through the DNA they carry which can activate TLR9 within endosomes. (114) Another possibility is recognition of the viral capsid, which can occur through both TLR-dependent and TLR-independent mechanisms. (115) The intracellular adaptor protein MyD88 has been shown to play a prominent role in invoking TLR-mediated immunogenicity with viral vectors being able to engage multiple MyD88 signaling pathways. (115)
The data from the phase I/II trials are summarized in Table 1. CanSino has already completed and published results for both their Phase I and II vaccines; the following will only present data from their Phase II trials. The biggest difference between the two trials is that CanSino removed the highest dose from their Phase I trials due to greater adverse events such as severe fever, fatigue, and muscle and joint pain. (21) Therefore, CanSino’s Phase II trial only tested the low and medium concentrations at 1 × 1011 and 5 × 1010 viral particles per dose in 253 and 129 patients, respectively. (22) By day 28, the 1 × 1011 group saw RBD-specific antibody GMT levels peak around 656.5 AU while the 5 × 1010 group peaked at around 571 AU. RBD-specific antibody seroconversion occurred in 96% and 97% of patients within the 1 × 1011 and 5 × 1010 groups, respectively. Seroconversion of NAbs occurred in fewer patients at 59 and 47% in the 1 × 1011 and 5 × 1010 groups, respectively. Antibodies were measured using ELISA assays. Neutralization was measured in vitro using a live SARS-CoV-2 virus as well as a pseudovirus.
Oxford/Astrazeneca only tested one dose at 5 × 1010 viral particles per dose (n = 533) but in a few patients (n = 10) also tested a booster of the same dose 28 days after the first. (23) Some of the patients were also prophylactically given a common anti-inflammatory drug, acetaminophen, and in those patients, there were fewer adverse events. Antibody concentrations against the SARS-CoV-2 S protein peaked at day 28 in the single-dose patients (157 AU), while the extra dose further improved response (639 AU within 56 days). The acetaminophen did not block generation of the antibody response. Depending on the neutralization assay used, the vaccine induced neutralizing titers from 62 to 100% of patients in the single-dose group and 100% in the double-dose patients. Both trials also documented moderate increases in T-cell responses as measured by ELISpot assays. (22,23)
Adverse events from both the Oxford/Astrazeneca and CanSino vaccines were varied from mild to moderate and did not warrant termination of either trial. The most prominent adverse effects in both the Oxford/Astrazeneca and CanSino trials were pain, fatigue, and headache (Table 1). Oxford/Astrazeneca did not test for other antibodies outside of IgG. (23) CanSino did test for IgM antibodies, but only against the nucleocapsid of SARS-CoV-2 to ensure that participants did not have previous exposure to the virus. (21) For advancement into Phase III clinical trials, CanSino noted that their lowest dose (5 × 1010 particles) demonstrated similar immunogenicity compared to their middle dose (1 × 1011 particles) while also reducing adverse events. (22) Thus, their Phase III trial will move forward at the lowest dose. They are set to begin testing in countries outside of China such as Saudi Arabia, where they already have an agreement to vaccinate 5,000 participants. (116) The company is looking to increase the number of participants by setting up clinical trials in other countries such as Russia, Brazil, and Chile. (116) Oxford/Astrazeneca will continue to test at its dose of 5 × 10, (10) but in its Brazil trials, will not test a prime boost. (117) This is most likely due to the similar immunogenicity and neutralization capability observed between the single dosed and double dosed groups. (23) They will also test in multiple countries with Phase III trials ongoing in Brazil, South Africa, and the United Kingdom. (23) Oxford/Astrazeneca will continue providing prophylactic acetaminophen for pain management. (117)

Discussion

ARTICLE SECTIONS
Jump To
SARS-CoV-2 has obligated global cooperation and teamwork as well as competition in fighting against the disease. The current vaccination efforts exemplify how the discovery and manufacturing of these vaccines is truly a worldwide effort that occurs within a context of commercial competition. BioNTech is based in Germany, Moderna and Pfizer are in the United States, CanSino is headquartered in China, Oxford is located in the United Kingdom, and Astrazeneca is headquartered in both the United Kingdom and Sweden. There are additional companies involved in clinical trials such as Bharat Biotech, Genexine, and Anges that are headquartered in India, South Korea, and Japan, respectively. (118−120) This is not an exhaustive list of all the countries working on a coronavirus vaccine, as there are other vaccine development efforts spanning the world (Table S1).
The need for vaccines against COVID-19 is so pressing that it is likely that unless one vaccine is much more effective than any other, multiple vaccine candidates will obtain approval in different locations. Generation of huge numbers of necessary doses will also favor production and sale by multiple companies. Multiple vaccine candidates from numerous countries will allow for wider and more rapid distribution to generate global “herd immunity”. Most or all of the vaccines are likely to be initially purchased by their countries’ government for distribution. Less developed countries are not involved in the vaccine effort, although they can be locations for vaccine testing if COVID-19 is prevalent. This is already evidenced by the Phase III clinical testing of CanSino and Oxford/Astrazeneca in Brazil and other countries. Distribution to developing countries may be highly influenced by vaccine design, price, and scalability. For instance, vaccines that require cold chain distribution or administration by health care professionals involve greater logistical challenges, especially in countries with limited resources. (116,117)
The race for a vaccine is also improved by the fact that there are many different vaccination nanotechnologies at play. Both BioNTech/Pfizer and Moderna are employing vaccination technologies in nucleic acid based vaccines that have not yet progressed beyond clinical trials for previous diseases. However, a key advantage of mRNA vaccines is their quick deployment and generation. In fact, Moderna was the first company to enter into clinical trials for COVID-19 vaccines in the United States and dosed the first patient in its Phase I study within 63 days of sequence selection. (8) The first batch of the vaccine was created within an impressive 25 days of sequence selection. In principle, mRNA vaccines allow an indefinite number of boosting regimens because the vaccine does not carry the antigen which could be blocked by an established neutralization response in seropositive individuals. (121) Furthermore, due to the antigen expression within the host, any in vivo post-translational modifications that occur are representative of the native antigen within the body. This is especially crucial for the S protein, which has up to 22 glycosylation sites within each protomer. (122) Areas of glycosylation can negate the neutralization capabilities of antibodies rendering vaccines ineffective even though high antibody titers are measured. Therefore, glycosylation is an important feature to consider when subunit vaccines are produced through heterologous expression. Nucleic acid based vaccines also activate the host’s immune system using multiple mechanisms eliciting both B and T-cell responses. (67) RNA can induce immune responses by activating both TLR3 and 7/8 for CD8+ T-cell activation as well as promote antibody production and CD4+ T-cell activation. (72) BioNTech/Pfizer explicitly mentions this in their manuscript. However, their RNA modification also reduces the immunogenicity of their RNA, which may dampen the adjuvant qualities of the RNA. It remains to be seen whether the increased translation capabilities from the RNA modification outweighs the decrease in immunogenicity. Compared to DNA vaccines, RNA vaccines do not require nuclear localization for antigen production allowing for activity once the RNA gains entry into the cell’s cytoplasm. (74) On the flip side, this also means that the expression is generally shorter lived and may require boosts while DNA vaccine immunogenicity can persist and may not require multiple dosing. (123,124) A potential way to boost the immune response would be the use of self-amplifying RNA that can replicate in vivo using replication machinery that is encoded into the vectors. (125) In fact, Imperial College London in a collaboration with Morningside Ventures has employed this approach for SARS-CoV-2 and is currently in Phase I/II of testing. (126) Furthermore, the half-life of unmodified RNA is very short due to rapid degradation within the body. (121) To help overcome this challenge, there are nucleotide modifications that can increase stability. Complexing the RNA with protamine also reduces RNase degradation while improving TLR-mediated adjuvant activity. (127,128) Both Moderna and BioNTech encapsulate their RNA within LNPs to help protect against degradation as well as employ chemical modifications to improve RNA stability. (17,19)
The nonreplicating viral vector vaccines have also made rapid progress in SARS-CoV-2 vaccination efforts. Both Oxford/Astrazeneca and CanSino have demonstrated safe but immunogenic vaccines warranting advancement into Phase III trials. These viral vectors have been investigated for many years, and technological advances have improved vector generation and large-scale production. Viral vector vaccines also possess inherent immunostimulatory profiles through both TLR-dependent and TLR-independent mechanisms. (62,68) In some instances, they can impart humoral responses as well as promote CD4+ and CD8+ T-cell responses even without the use of another adjuvant; (70) ELISpot assays demonstrated significant T-cell response activation in both the Oxford/Astrazeneca and CanSino trials. (22,23) Another benefit is that viral vectors can enter into dendritic cells (DCs) leading to enhanced antigen presentation and immune cell activation. They can also function after entry into both actively dividing and quiescent cells leading to wide tissue tropism. (129) However, this tropism can also induce more severe side effects.
Humans have been widely exposed to human Ads leading to pre-existing immunity against some Ad vectors, which may impact the effectiveness of the vaccines. Indeed, CanSino noted that 52% of their participants had high pre-existing immunity to Ad5. (22) The 48% of participants that had low pre-existing immunity generated two times the levels of NAbs- and RBD-specific antibodies than the higher pre-existing immunity group, suggesting that pre-existing immunity to the viral vector impairs response to the vaccine. Oxford/Astrazeneca circumvents this issue by using a chimpanzee Ad, where seroprevalence rates are much lower in humans. Oxford/Astrazenca only detected NAbs against the chimpanzee viral vector in one of 98 patients. (23) There are other ways to thwart the issue of pre-existing immunity. For instance, much of the pre-existing immunity generated from Ad is derived from the hypervariable regions of its hexon protein. (130) Genetic modifications of the hypervariable regions as well as to another structural protein, the fiber knob domain, can reduce neutralization. (70) Lastly, Ads infect a wide range of animals from birds and reptiles to bats, and similarly to Oxford/Astrazeneca utilizing less prevalent chimpanzee Ad vectors, one can imagine the repurposing of other Ad viral vectors. (129) Other nonhuman Ad vectors that have been investigated in the past include porcine, bovine, canine, ovine, and fowl viral vectors. (131−133) All of the viral vectors noted above are nonpathogenic toward humans, but can infect mammalian cells, and some–such as the bovine viral vector–are naturally replication deficient imparting high safety. (134−137)

Other Companies in Advanced Clinical Trials

Outside the four major companies discussed above, there are a small number of other companies that have moved beyond initial clinical trials and are now investigating more extensive clinical trials either in Phase II or III. These companies have not published their data but have announced positive results in their trials with press releases and statements. Some of the companies are currently preparing the data for publication. The following information is summarized in both Table 1 and Table 2. Sinovac Biotech and Sinopharm are two of those companies, and they both employ an inactivated form of the virus. (138,139) Inactivated vaccines are well-established and are produced through chemical or heat treatment leading to replication-deficient vaccines. (62) Sinopharm’s vaccine has already received emergency authorization in China for employees in state-owned businesses that require global traveling. (139) The company has two products in clinical testing developed by either the Wuhan Institute of Biological Products or the Beijing Institute of Biological Products. The Institute of Medical Biology, Chinese Academy of Medical Sciences is developing another inactivated vaccine and has progressed into Phase II clinical trials, but there is no public information about the clinical trials or the vaccine. (140) Two other companies, Inovio Pharmaceuticals and Zydus Cadila, have recently completed their Phase I testing citing favorable safety results. (82,141) Inovio additionally announced induction of both T-cell and humoral responses. (82) Inovio and Zydus Cadila produce nucleic-acid based vaccines, but unlike Moderna and BioNTech/Pfizer, utilize DNA rather than RNA. Anhui Zhifei Longcom Biopharmaceutical and the Institute of Microbiology of the Chinese Academy of Sciences are codeveloping a subunit vaccine that has moved into Phase II testing, but there have been no public announcements of the trial. (91) The vaccine consists of an RBD dimer from SARS-CoV-2 administered with an adjuvant. (7) Novavax is another subunit vaccine developer that has recently released positive data from their Phase I/II trial, which also had a reassuring safety profile. (18) They employ a full-length S protein subunit vaccine administered with their patented saponin-based Matrix-M adjuvant. The recombinant S protein is generated with mutations at the S1 and S2 cleavage site to protect against protease degradation and additional proline substitutions at the heptad repeat1/central helix to keep the protein in its prefusion conformation. The S protein and Matrix-M adjuvant are mixed together right before injection. (142) The vaccine led to antibody neutralization titers in all patients both against the S protein (after one dose) as well as to the wild-type virus (after two doses). Vaxine announced positive safety data as the latest subunit vaccine that has entered into advanced clinical trials. (94) The vaccine was developed using computer modeling to identify epitopes that may block the S protein from binding to the ACE2 receptor. (112)
The Gamaleya Research Institute based in Russia has been developing nonreplicating Ad vector vaccines. (7) The vaccine consists of two vectors, Ad5 and Ad26. (89,90,143) The vaccine became the first “registered” vaccine in the world, although reports show that only Phase II clinical trials have been completed on a few hundred participants. (111,144) The company has coordinated with the Russian government to skip standard phase III clinical trials, and instead, phase III trials will be held in parallel with broad vaccination efforts. To the best of our knowledge, the results from the phase II clinical trials have not been made public. Even without any public information, Russian officials have stated that they have garnered interest from 20 outside countries with preorders of over a billion doses. (145) Russia plans on mass-producing the vaccine for immediate countrywide vaccination of frontline medical workers and teachers followed by vaccination of the general public in the fall.

Adjuvant Use

Many of the aforementioned vaccines may require the use of an adjuvant to stimulate response against the antigen; however, discussion of the adjuvant is often overlooked. Of the companies addressed in this review, only Anhui Zhifei Longcom, Novavax, Sinovac, and Vaxine explicitly mention the use of an adjuvant. (7,18) Novavax’s adjuvant, Matrix-M, boosts vaccine immunogenicity by recruiting APCs to the site of injection thereby increasing antigen presentation to T-cells within draining lymph nodes. (18) The Advax adjuvant used by Vaxine is a polysaccharide microparticle derived from polyfructofuranosyl-d-glucose, and unlike many other adjuvants, Advax boosts the intrinsic immunostimulatory nature of the antigen. (146) In an influenza split vaccine with a Th2 antigen, Advax acted as a Th2 adjuvant, while in an influenza inactivated antigen with a Th1 antigen, it acted as a Th1 adjuvant. To the best of our knowledge, there is no public information on the adjuvant used by Anhui Zhifei Longcom.
BioNTech/Pfizer and Moderna do not explicitly state the use of an adjuvant within their vaccines, but RNA already contains immunostimulatory properties and signals through pathogen recognition receptors. (72) It remains to be seen whether the immunostimulation from RNA is strong enough to confer full protection against SARS-CoV-2. There is also a possibility that the LNP carriers they utilize confer adjuvant properties themselves. Since the discovery that liposomes incorporating dicetyl phosphate provided greater protection against diphtheria toxoid than unmodified liposomes, the study of using lipid carriers also as adjuvants has grown considerably. (101) Unilamellar phospholipid membrane nanoparticles encapsulating viral antigens (otherwise known as virosomes) with adjuvant properties against influenza and hepatitis A are currently already used in the clinic. (147)
Other companies such as GlaxoSmithKline (GSK) and Dynavax have offered their own adjuvants to be tested in combination with different vaccines. (7) GSK’s adjuvant system (AS03) consists of α-tocopherol, squalene, and polysorbate 80 in an oil-in-water emulsion and helps boost antigen-specific antibody production by increasing antigen uptake and presentation within lymph nodes. (148) Its adjuvant was utilized previously in the 2009 H1N1 pandemic. Currently, GSK is offering AS03 in collaboration with Clover Biopharmaceuticals (149) and Medicago, (150) which are both in Phase I clinical testing, and Sanofi (151) and Innovax, (152) which remain in preclinical trials. GSK has additionally offered its adjuvant technology to the Coalition for Epidemic Preparedness Innovation, which helped fund companies such as Moderna and Inovio. (153) The Dynavax adjuvant (CpG 1018) is composed of a 22-mer oligonucleotide sequence with the ability to stimulate the TLR9 pathogen recognition receptor for improved CD4+ and CD8+ responses as well as formation of B and T-cell memory. (154) This adjuvant has been utilized with its hepatitis B vaccine for improved antibody response. Dynavax has also partnered with Clover (149) and Medicago (150) as well as Medigen Vaccine, (155) which just entered into Phase I clinical testing. Additionally, Dynavax has offered its adjuvant to Sinovac (156) and Valneva, (157) which remain in the preclinical stage.
As discussed in an earlier section, nanoparticles offer opportunities for codelivery of antigen and adjuvant to target lymph nodes and APCs, and an increasing body of data suggests that codelivery of antigen and adjuvant improves potency of the vaccines at lower doses and reduces side effects. (52,53) BioNTech/Pfizer claims that the mRNA within their vaccines acts as its own adjuvant enabling codelivery of antigen and adjuvant. (19) The viral vectors by Oxford/Astrazeneca and CanSino as well as the viral DNA may act as adjuvants as well. (114,115) However, neither mRNA nor viral vector vaccines have successfully translated into the clinic, and it is clear that more research is needed to fully understand the potential and limitations of the various nanotechnology platforms in vaccine development.

Conclusion

ARTICLE SECTIONS
Jump To
There are over a hundred vaccines being developed throughout the world, and the race to be the first effective vaccine has fueled the rapid development of both preclinical and currently utilized vaccine approaches. There is no “one-size-fits-all” solution as each vaccine strategy has both advantages and disadvantages. Of the leading companies, Moderna, BioNTech/Pfizer, and Inovio are producing nucleic acid based vaccines, and early studies from Moderna and BioNTech/Pfizer generated strong antibody. Ad-based vaccines remain early frontrunners as well, with Oxford/Astrazeneca and CanSino likewise publishing favorable early data. Other state-run institutions and companies such as the Gamaleya Research Institute and Sinopharm have advanced further into their respective Phases of clinical trials and have been granted emergency use by their respective countries. Due to the generation of so many vaccines within many different countries, there will potentially be more than one effective vaccine, and it is crucial that effective vaccines are distributed to all parts of the world to generate global herd immunity. Regardless of the first developer, it is of truly noteworthy importance that the global effort to develop, test, produce, and distribute effective vaccines is being done so rapidly. Success in this effort will not only lead to an end to the pandemic, but what is learned will aid in future research and development efforts as well as the implementation of previously unused vaccine types for future diseases.

Supporting Information

ARTICLE SECTIONS
Jump To

The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acsnano.0c07197.

  • Data table summarizing COVID-19 vaccines and their type, developer, and status (Table S1) (PDF)

Terms & Conditions

Most electronic Supporting Information files are available without a subscription to ACS Web Editions. Such files may be downloaded by article for research use (if there is a public use license linked to the relevant article, that license may permit other uses). Permission may be obtained from ACS for other uses through requests via the RightsLink permission system: http://pubs.acs.org/page/copyright/permissions.html.

Author Information

ARTICLE SECTIONS
Jump To
  • Corresponding Authors
    • Steven N. Fiering - Geisel School of Medicine, Dartmouth College, Hanover, New Hampshire 03755, United States;  Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire 03766, United States;  Email: [email protected]
    • Nicole F. Steinmetz - Department of Bioengineering, University of California San Diego, La Jolla, California 92093, United States;  Department of NanoEngineering, University of California San Diego, La Jolla, California 92093, United States;  Department of Radiology, University of California San Diego, La Jolla, California 92093, United States;  Moores Cancer Center, University of California San Diego, La Jolla, California 92093, United States;  Center for Nano-ImmunoEngineering, University of California San Diego, La Jolla, California 92093, United States;  Orcidhttp://orcid.org/0000-0002-0130-0481;  Email: [email protected]
  • Authors
    • Young Hun Chung - Department of Bioengineering, University of California San Diego, La Jolla, California 92093, United States;  Orcidhttp://orcid.org/0000-0002-6578-8076
    • Veronique Beiss - Department of NanoEngineering, University of California San Diego, La Jolla, California 92093, United States
  • Notes
    The authors declare the following competing financial interest(s): Drs. Fiering and Steinmetz are co-founders of and have a financial interest in Mosaic Immunoengineering Inc. The other authors declare no potential conflict of interest.

Acknowledgments

ARTICLE SECTIONS
Jump To

Dr. Soo Khim Chan is thanked for help in compiling the data for Table S1.This work is supported by a grant from the National Science Foundation NSF CMMI-2027668 (to NFS).

Vocabulary

ARTICLE SECTIONS
Jump To
vaccine

a substance that produces an immune response in the host protecting the host against pathogens
nucleic acid vaccine

vaccine type utilizing either mRNA or DNA that encode viral antigens
viral vector vaccine

vaccine type with DNA encoding the viral antigens of the target pathogen, viral vectors can be nonreplicating or replicating
inactivated vaccine

well-established vaccine type where the native virus is inactivated with heat or chemical treatment
subunit vaccine

vaccine type utilizing portions of the virus as antigens to produce an immune response
adjuvant

an additional immunostimulatory reagent administered alongside the antigen to boost immune responses

References

ARTICLE SECTIONS
Jump To

This article references 157 other publications.

  1. 1
    Cascella, M.; Rajnik, M.; Cuomo, A.; Dulebohn, S. C.; Di Napoli, R. Features, Evaluation and Treatment Coronavirus (COVID-19). In StatPearls; StatPearls Publishing: Treasure Island (FL), 2020.
    Google Scholar
    There is no corresponding record for this reference.
  2. 2
    Astuti, I. Ysrafil. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): An Overview of Viral Structure and Host Response. Diabetes Metab Syndr 2020, 14, 407– 412,  DOI: 10.1016/j.dsx.2020.04.020
    Google Scholar
    2
    Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): An overview of viral structure and host response
    Astuti Indwiani; Ysrafil
    Diabetes & metabolic syndrome (2020), 14 (4), 407-412 ISSN:.
    BACKGROUND AND AIM: As a result of its rapid spread in various countries around the world, on March 11, 2020, WHO issued an announcement of the change in coronavirus disease 2019 status from epidemic to pandemic disease. The virus that causes this disease is indicated originating from animals traded in a live animal market in Wuhan, China. Severe Acute Respiratory Syndrome Coronavirus 2 can attack lung cells because there are many conserved receptor entries, namely Angiotensin Converting Enzyme-2. The presence of this virus in host cells will initiate various protective responses leading to pneumonia and Acute Respiratory Distress Syndrome. This review aimed to provide an overview related to this virus and examine the body's responses and possible therapies. METHOD: We searched PubMed databases for Severe Acute Respiratory Syndrome Coronavirus-2, Middle East respiratory syndrome-related coronavirus and Severe Acute Respiratory Syndrome Coronavirus. Full texts were retrieved, analyzed and developed into an easy-to-understand review. RESULTS: We provide a complete review related to structure, origin, and how the body responds to this virus infection and explain the possibility of an immune system over-reaction or cytokine storm. We also include an explanation of how this virus creates modes of avoidance to evade immune system attacks. We further explain the therapeutic approaches that can be taken in the treatment and prevention of this viral infection. CONCLUSION: In summary, based on the structural and immune-evasion system of coronavirus, we suggest several approaches to treat the disease.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB38zps12nsw%253D%253D&md5=a417c9c08407e769309a5f530b719587
  3. 3
    WHO Coronavirus Disease (COVID-19) Dashboard https://covid19.who.int (accessed 2020-08-3).
    Google Scholar
    There is no corresponding record for this reference.
  4. 4
    Washington, D. of C. 1100 C. A. N. S. 1300B; Dc 20036. PolitiFact - Cuomo Accurately Says that Other Countries that Reopened Saw an Increase in Coronavirus Infections. https://www.politifact.com/factchecks/2020/apr/20/andrew-cuomo/cuomo-accurately-says-other-countries-reopened-saw/ (accessed 2020-08-03).
    Google Scholar
    There is no corresponding record for this reference.
  5. 5
    Kissler, S. M.; Tedijanto, C.; Goldstein, E.; Grad, Y. H.; Lipsitch, M. Projecting the Transmission Dynamics of SARS-CoV-2 through the Postpandemic Period. Science 2020, 368, 860– 868,  DOI: 10.1126/science.abb5793
    Google Scholar
    5
    Projecting the transmission dynamics of SARS-CoV-2 through the postpandemic period
    Kissler, Stephen M.; Tedijanto, Christine; Goldstein, Edward; Grad, Yonatan H.; Lipsitch, Marc
    Science (Washington, DC, United States) (2020), 368 (6493), 860-868CODEN: SCIEAS; ISSN:1095-9203. (American Association for the Advancement of Science)
    It is urgent to understand the future of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) transmission. We used ests. of seasonality, immunity, and cross-immunity for human coronavirus OC43 (HCoV-OC43) and HCoV-HKU1 using time-series data from the United States to inform a model of SARS-CoV-2 transmission. We projected that recurrent wintertime outbreaks of SARS-CoV-2 will probably occur after the initial, most severe pandemic wave. Absent other interventions, a key metric for the success of social distancing is whether crit. care capacities are exceeded. To avoid this, prolonged or intermittent social distancing may be necessary into 2022. Addnl. interventions, including expanded crit. care capacity and an effective therapeutic, would improve the success of intermittent distancing and hasten the acquisition of herd immunity. Longitudinal serol. studies are urgently needed to det. the extent and duration of immunity to SARS-CoV-2. Even in the event of apparent elimination, SARS-CoV-2 surveillance should be maintained because a resurgence in contagion could be possible as late as 2024.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhtVWnur%252FI&md5=3837e7a844f54a14bfc71f8dd1042b3a
  6. 6
    Wu, A.; Peng, Y.; Huang, B.; Ding, X.; Wang, X.; Niu, P.; Meng, J.; Zhu, Z.; Zhang, Z.; Wang, J.; Sheng, J.; Quan, L.; Xia, Z.; Tan, W.; Cheng, G.; Jiang, T. Genome Composition and Divergence of the Novel Coronavirus (2019-NCoV) Originating in China. Cell Host Microbe 2020, 27, 325– 328,  DOI: 10.1016/j.chom.2020.02.001
    Google Scholar
    6
    Genome Composition and Divergence of the Novel Coronavirus (2019-nCoV) Originating in China
    Wu, Aiping; Peng, Yousong; Huang, Baoying; Ding, Xiao; Wang, Xianyue; Niu, Peihua; Meng, Jing; Zhu, Zhaozhong; Zhang, Zheng; Wang, Jiangyuan; Sheng, Jie; Quan, Lijun; Xia, Zanxian; Tan, Wenjie; Cheng, Genhong; Jiang, Taijiao
    Cell Host & Microbe (2020), 27 (3), 325-328CODEN: CHMECB; ISSN:1931-3128. (Elsevier Inc.)
    An in-depth annotation of the newly discovered coronavirus (2019-nCoV) genome has revealed differences between 2019-nCoV and severe acute respiratory syndrome (SARS) or SARS-like coronaviruses. A systematic comparison identified 380 amino acid substitutions between these coronaviruses, which may have caused functional and pathogenic divergence of 2019-nCoV.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXivVeiu7s%253D&md5=3c036a5fdc31fae6e87fd2754c5018fc
  7. 7
    Draft Landscape of COVID-19 Candidate Vaccines. https://www.who.int/publications/m/item/draft-landscape-of-covid-19-candidate-vaccines (accessed 2020-08-03).
    Google Scholar
    There is no corresponding record for this reference.
  8. 8
    Moderna’s Work on a COVID-19 Vaccine Candidate, Moderna, Inc. https://www.modernatx.com/modernas-work-potential-vaccine-against-covid-19 (accessed 2020-08-03).
    Google Scholar
    There is no corresponding record for this reference.
  9. 9
    Chinese Clinical Trial Register (ChiCTR) - The World Health Organization International Clinical Trials Registered Organization Registered Platform. http://www.chictr.org.cn/showprojen.aspx?proj=52227 (accessed 2020-05-06).
    Google Scholar
    There is no corresponding record for this reference.
  10. 10
    Phase I, Open-Label, Dose-Ranging Study of the Safety and Immunogenicity of 2019-NCoV Vaccine (MRNA-1273) in Healthy Adults - Full Text View. ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT04283461 (accessed 2020-04-01).
    Google Scholar
    There is no corresponding record for this reference.
  11. 11
    Kim, Y. C.; Dema, B.; Reyes-Sandoval, A. COVID-19 Vaccines: Breaking Record Times to First-in-Human Trials. NPJ. Vaccines 2020,  DOI: 10.1038/s41541-020-0188-3
    Google Scholar
    There is no corresponding record for this reference.
  12. 12
    Singh, K.; Mehta, S. The Clinical Development Process for a Novel Preventive Vaccine: An Overview. J. Postgrad. Med. 2016, 62, 4– 11,  DOI: 10.4103/0022-3859.173187
    Google Scholar
    12
    The clinical development process for a novel preventive vaccine: An overview
    Singh K; Mehta S
    Journal of postgraduate medicine (2016), 62 (1), 4-11 ISSN:.
    Each novel vaccine candidate needs to be evaluated for safety, immunogenicity, and protective efficacy in humans before it is licensed for use. After initial safety evaluation in healthy adults, each vaccine candidate follows a unique development path. This article on clinical development gives an overview on the development path based on the expectations of various guidelines issued by the World Health Organization (WHO), the European Medicines Agency (EMA), and the United States Food and Drug Administration (USFDA). The manuscript describes the objectives, study populations, study designs, study site, and outcome(s) of each phase (Phase I-III) of a clinical trial. Examples from the clinical development of a malaria vaccine candidate, a rotavirus vaccine, and two vaccines approved for human papillomavirus (HPV) have also been discussed. The article also tabulates relevant guidelines, which can be referred to while drafting the development path of a novel vaccine candidate.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC28rnsVyjsQ%253D%253D&md5=49266943984be754033f61421d4ba6be
  13. 13
    Lee, W. S.; Wheatley, A. K.; Kent, S. J.; DeKosky, B. J. Antibody-Dependent Enhancement and SARS-CoV-2 Vaccines and Therapies. Nat. Microbiol. 2020, 5, 1185– 1191,  DOI: 10.1038/s41564-020-00789-5
    Google Scholar
    13
    Antibody-dependent enhancement and SARS-CoV-2 vaccines and therapies
    Lee, Wen Shi; Wheatley, Adam K.; Kent, Stephen J.; DeKosky, Brandon J.
    Nature Microbiology (2020), 5 (10), 1185-1191CODEN: NMAICH; ISSN:2058-5276. (Nature Research)
    A review. Antibody-based drugs and vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are being expedited through preclin. and clin. development. Data from the study of SARS-CoV and other respiratory viruses suggest that anti-SARS-CoV-2 antibodies could exacerbate COVID-19 through antibody-dependent enhancement (ADE). Previous respiratory syncytial virus and dengue virus vaccine studies revealed human clin. safety risks related to ADE, resulting in failed vaccine trials. Here, the authors describe key ADE mechanisms and discuss mitigation strategies for SARS-CoV-2 vaccines and therapies in development. The authors also outline recently published data to evaluate the risks and opportunities for antibody-based protection against SARS-CoV-2.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhvVyqurzJ&md5=d42e108c864dd793b68f21b459c304d0
  14. 14
    Schlake, T.; Thess, A.; Fotin-Mleczek, M.; Kallen, K.-J. Developing MRNA-Vaccine Technologies. RNA Biol. 2012, 9, 1319– 1330,  DOI: 10.4161/rna.22269
    Google Scholar
    14
    Developing mRNA-vaccine technologies
    Schlake, Thomas; Thess, Andreas; Fotin-Mleczek, Mariola; Kallen, Karl-Josef
    RNA Biology (2012), 9 (11), 1319-1330CODEN: RBNIBE; ISSN:1547-6286. (Landes Bioscience)
    A review. MRNA vaccines combine desirable immunol. properties with an outstanding safety profile and the unmet flexibility of genetic vaccines. Based on in situ protein expression, mRNA vaccines are capable of inducing a balanced immune response comprising both cellular and humoral immunity while not subject to MHC haplotype restriction. In addn., mRNA is an intrinsically safe vector as it is a minimal and only transient carrier of information that does not interact with the genome. Because any protein can be expressed from mRNA without the need to adjust the prodn. process, mRNA vaccines also offer max. flexibility with respect to development. Taken together, mRNA presents a promising vector that may well become the basis of a game-changing vaccine technol. platform. Here, we outline the current knowledge regarding different aspects that should be considered when developing an mRNA-based vaccine technol.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXjsFKktL8%253D&md5=5f3132e37cbf0b27ea1e128869d6dd11
  15. 15
    Dance, A. Coronavirus Vaccines Get a Biotech Boost. Nature 2020, 583, 647– 649,  DOI: 10.1038/d41586-020-02154-2
    Google Scholar
    15
    Coronavirus vaccines get a biotech boost
    Dance, Amber
    Nature (London, United Kingdom) (2020), 583 (7817), 647-649CODEN: NATUAS; ISSN:0028-0836. (Nature Research)
    Advances in technol. are accelerating the search for drugs to arm the immune system against SARS-CoV-2.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhsVahu7bE&md5=3bc5aa5ffd099cce41c163852b380651
  16. 16
    Thomas, K. U.S. Will Pay $1.6 Billion to Novavax for Coronavirus Vaccine. New York Times 2020, July 7.
    Google Scholar
    There is no corresponding record for this reference.
  17. 17
    Jackson, L. A.; Anderson, E. J.; Rouphael, N. G.; Roberts, P. C.; Makhene, M.; Coler, R. N.; McCullough, M. P.; Chappell, J. D.; Denison, M. R.; Stevens, L. J.; Pruijssers, A. J.; McDermott, A.; Flach, B.; Doria-Rose, N. A.; Corbett, K. S.; Morabito, K. M.; O’Dell, S.; Schmidt, S. D.; Swanson, P. A.; Padilla, M. An MRNA Vaccine against SARS-CoV-2 — Preliminary Report. N. Engl. J. Med. 2020, 0, null,  DOI: 10.1056/NEJMoa2022483
    Google Scholar
    There is no corresponding record for this reference.
  18. 18
    Novavax Announces Positive Phase 1 Data for Its COVID-19 Vaccine Candidate, Novavax Inc. IR Site. https://ir.novavax.com/news-releases/news-release-details/novavax-announces-positive-phase-1-data-its-covid-19-vaccine (accessed 2020-08-06).
    Google Scholar
    There is no corresponding record for this reference.
  19. 19
    Mulligan, M. J.; Lyke, K. E.; Kitchin, N.; Absalon, J.; Gurtman, A.; Lockhart, S. P.; Neuzil, K.; Raabe, V.; Bailey, R.; Swanson, K. A.; Li, P.; Koury, K.; Kalina, W.; Cooper, D.; Fonter-Garfias, C.; Shi, P.-Y.; Tuereci, O.; Tompkins, K. R.; Walsh, E. E.; Frenck, R., Phase 1/2 Study to Describe the Safety and Immunogenicity of a COVID-19 RNA Vaccine Candidate (BNT162b1) in Adults 18 to 55 Years of Age: Interim Report. medRxiv . 2020 2020.06.30.20142570.https://www.medrxiv.org/content/10.1101/2020.06.30.20142570v1.article-info (accessed 2020-08-06).
    Google Scholar
    There is no corresponding record for this reference.
  20. 20
    Sahin, U.; Muik, A.; Derhovanessian, E.; Vogler, I.; Kranz, L. M.; Vormehr, M.; Baum, A.; Pascal, K.; Quandt, J.; Maurus, D.; Brachtendorf, S.; Loerks, V. L.; Sikorski, J.; Hilker, R.; Becker, D.; Eller, A.-K.; Gruetzner, J.; Boesler, C.; Rosenbaum, C.; Kuehnle, M.-C., Concurrent Human Antibody and TH1 Type T-Cell Responses Elicited by a COVID-19 RNA Vaccine. medRxiv 2020, 2020.07.17.20140533. https://www.medrxiv.org/content/10.1101/2020.07.17.20140533v1.article-info (accessed 2020-08-06).
    Google Scholar
    There is no corresponding record for this reference.
  21. 21
    Zhu, F.-C.; Li, Y.-H.; Guan, X.-H.; Hou, L.-H.; Wang, W.-J.; Li, J.-X.; Wu, S.-P.; Wang, B.-S.; Wang, Z.; Wang, L.; Jia, S.-Y.; Jiang, H.-D.; Wang, L.; Jiang, T.; Hu, Y.; Gou, J.-B.; Xu, S.-B.; Xu, J.-J.; Wang, X.-W.; Wang, W. Safety, Tolerability, and Immunogenicity of a Recombinant Adenovirus Type-5 Vectored COVID-19 Vaccine: A Dose-Escalation, Open-Label, Non-Randomised, First-in-Human Trial. Lancet 2020, 395, 1845– 1854,  DOI: 10.1016/S0140-6736(20)31208-3
    Google Scholar
    21
    Safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 vectored COVID-19 vaccine: a dose-escalation, open-label, non-randomised, first-in-human trial
    Zhu, Feng-Cai; Li, Yu-Hua; Guan, Xu-Hua; Hou, Li-Hua; Wang, Wen-Juan; Li, Jing-Xin; Wu, Shi-Po; Wang, Bu-Sen; Wang, Zhao; Wang, Lei; Jia, Si-Yue; Jiang, Hu-Dachuan; Wang, Ling; Jiang, Tao; Hu, Yi; Gou, Jin-Bo; Xu, Sha-Bei; Xu, Jun-Jie; Wang, Xue-Wen; Wang, Wei; Chen, Wei
    Lancet (2020), 395 (10240), 1845-1854CODEN: LANCAO; ISSN:0140-6736. (Elsevier Ltd.)
    A vaccine to protect against COVID-19 is urgently needed. We aimed to assess the safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 (Ad5) vectored COVID-19 vaccine expressing the spike glycoprotein of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strain. We did a dose-escalation, single-center, open-label, non-randomized, phase 1 trial of an Ad5 vectored COVID-19 vaccine in Wuhan, China. Healthy adults 18-60 yr were sequentially enrolled and allocated to 1 of 3 dose groups (5 × 1010, 1 × 1011, and 1.5 × 1011 viral particles) to receive an i.m. injection of vaccine. The primary outcome was adverse events in the 7 days post-vaccination. Safety was assessed over 28 days post-vaccination. Specific antibodies were measured with ELISA, and the neutralizing antibody responses induced by vaccination were detected with SARS-CoV-2 virus neutralization and pseudovirus neutralization tests. T-cell responses were assessed by enzyme-linked immunospot and flow-cytometry assays. This study is registered with ClinicalTrials.gov, NCT04313127. Between March 16 and March 27, 2020, we screened 195 individuals for eligibility. Of them, 108 participants (51% male, 49% female; mean age 36.3 yr) were recruited and received the low dose (n=36), middle dose (n=36), or high dose (n=36) of the vaccine. All enrolled participants were included in the anal. At least 1 adverse reaction within the 1st 7 days after the vaccination was reported in 30 (83%) participants in the low dose group, 30 (83%) participants in the middle dose group, and 27 (75%) participants in the high dose group. The most common injection site adverse reaction was pain, which was reported in 58 (54%) vaccine recipients, and the most commonly reported systematic adverse reactions were fever (50 [46%]), fatigue (47 [44%]), headache (42 [39%]), and muscle pain (18 [17%]). Most adverse reactions that were reported in all dose groups were mild or moderate in severity. No serious adverse event was noted within 28 days post-vaccination. ELISA antibodies and neutralizing antibodies increased significantly at day 14, and peaked 28 days post-vaccination. Specific T-cell response peaked at day 14 post-vaccination. The Ad5 vectored COVID-19 vaccine is tolerable and immunogenic at 28 days post-vaccination. Humoral responses against SARS-CoV-2 peaked at day 28 post-vaccination in healthy adults, and rapid specific T-cell responses were noted from day 14 post-vaccination. Our findings suggest that the Ad5 vectored COVID-19 vaccine warrants further investigation.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhtVSjtrvO&md5=a14ff6459d359bd1743e3549191b3508
  22. 22
    Zhu, F.-C.; Guan, X.-H.; Li, Y.-H.; Huang, J.-Y.; Jiang, T.; Hou, L.-H.; Li, J.-X.; Yang, B.-F.; Wang, L.; Wang, W.-J.; Wu, S.-P.; Wang, Z.; Wu, X.-H.; Xu, J.-J.; Zhang, Z.; Jia, S.-Y.; Wang, B.-S.; Hu, Y.; Liu, J.-J.; Zhang, J. Immunogenicity and Safety of a Recombinant Adenovirus Type-5-Vectored COVID-19 Vaccine in Healthy Adults Aged 18 Years or Older: A Randomised, Double-Blind, Placebo-Controlled, Phase 2 Trial. Lancet 2020, 396, 479– 488,  DOI: 10.1016/S0140-6736(20)31605-6
    Google Scholar
    22
    Immunogenicity and safety of a recombinant adenovirus type-5-vectored COVID-19 vaccine in healthy adults aged 18 years or older: a randomised, double-blind, placebo-controlled, phase 2 trial
    Zhu, Feng-Cai; Guan, Xu-Hua; Li, Yu-Hua; Huang, Jian-Ying; Jiang, Tao; Hou, Li-Hua; Li, Jing-Xin; Yang, Bei-Fang; Wang, Ling; Wang, Wen-Juan; Wu, Shi-Po; Wang, Zhao; Wu, Xiao-Hong; Xu, Jun-Jie; Zhang, Zhe; Jia, Si-Yue; Wang, Bu-Sen; Hu, Yi; Liu, Jing-Jing; Zhang, Jun; Qian, Xiao-Ai; Li, Qiong; Pan, Hong-Xing; Jiang, Hu-Dachuan; Deng, Peng; Gou, Jin-Bo; Wang, Xue-Wen; Wang, Xing-Huan; Chen, Wei
    Lancet (2020), 396 (10249), 479-488CODEN: LANCAO; ISSN:0140-6736. (Elsevier Ltd.)
    This is the first randomised controlled trial for assessment of the immunogenicity and safety of a candidate non-replicating adenovirus type-5 (Ad5)-vectored COVID-19 vaccine, aiming to det. an appropriate dose of the candidate vaccine for an efficacy study. This randomised, double-blind, placebo-controlled, phase 2 trial of the Ad5-vectored COVID-19 vaccine was done in a single center in Wuhan, China. Healthy adults aged 18 years or older, who were HIV-neg. and previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-free, were eligible to participate and were randomly assigned to receive the vaccine at a dose of 1 x 1011 viral particles per mL or 5 x 1010 viral particles per mL, or placebo. Investigators allocated participants at a ratio of 2:1:1 to receive a single injection i.m. in the arm. The randomisation list (block size 4) was generated by an independent statistician. Participants, investigators, and staff undertaking lab. analyses were masked to group allocation. The primary endpoints for immunogenicity were the geometric mean titers (GMTs) of specific ELISA antibody responses to the receptor binding domain (RBD) and neutralising antibody responses at day 28. The primary endpoint for safety evaluation was the incidence of adverse reactions within 14 days. All recruited participants who received at least one dose were included in the primary and safety analyses. This study is registered with ClinicalTrials.gov, NCT04341389.603 volunteers were recruited and screened for eligibility between Apr. 11 and 16, 2020. 508 eligible participants (50% male; mean age 39·7 years, SD 12·5) consented to participate in the trial and were randomly assigned to receive the vaccine (1 x 1011 viral particles n=253; 5 x 1010 viral particles n=129) or placebo (n=126). In the 1 x 1011 and 5 x 1010 viral particles dose groups, the RBD-specific ELISA antibodies peaked at 656·5 (95% CI 575·2-749·2) and 571·0 (467·6-697·3), with seroconversion rates at 96% (95% CI 93-98) and 97% (92-99), resp., at day 28. Both doses of the vaccine induced significant neutralising antibody responses to live SARS-CoV-2, with GMTs of 19·5 (95% CI 16·8-22·7) and 18·3 (14·4-23·3) in participants receiving 1 x 1011 and 5 x 1010 viral particles, resp. Specific interferon γ enzyme-linked immunospot assay responses post vaccination were obsd. in 227 (90%, 95% CI 85-93) of 253 and 113 (88%, 81-92) of 129 participants in the 1 x 1011 and 5 x 1010 viral particles dose groups, resp. Solicited adverse reactions were reported by 183 (72%) of 253 and 96 (74%) of 129 participants in the 1 x 1011 and 5 x 1010 viral particles dose groups, resp. Severe adverse reactions were reported by 24 (9%) participants in the 1 x 1011 viral particles dose group and one (1%) participant in the 5 x 1010 viral particles dose group. No serious adverse reactions were documented. The Ad5-vectored COVID-19 vaccine at 5 x 1010 viral particles is safe, and induced significant immune responses in the majority of recipients after a single immunization. National Key R&D Program of China, National Science and Technol. Major Project, and CanSino Biologics.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhsVarsr7K&md5=29aae4e8cc67aa9c89c44be96c42f82d
  23. 23
    Folegatti, P. M.; Ewer, K. J.; Aley, P. K.; Angus, B.; Becker, S.; Belij-Rammerstorfer, S.; Bellamy, D.; Bibi, S.; Bittaye, M.; Clutterbuck, E. A.; Dold, C.; Faust, S. N.; Finn, A.; Flaxman, A. L.; Hallis, B.; Heath, P.; Jenkin, D.; Lazarus, R.; Makinson, R.; Minassian, A. M. Safety and Immunogenicity of the ChAdOx1 NCoV-19 Vaccine against SARS-CoV-2: A Preliminary Report of a Phase 1/2, Single-Blind, Randomised Controlled Trial. Lancet 2020, 396, 467– 478,  DOI: 10.1016/S0140-6736(20)31604-4
    Google Scholar
    23
    Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial
    Folegatti, Pedro M.; Ewer, Katie J.; Aley, Parvinder K.; Angus, Brian; Becker, Stephan; Belij-Rammerstorfer, Sandra; Bellamy, Duncan; Bibi, Sagida; Bittaye, Mustapha; Clutterbuck, Elizabeth A.; Dold, Christina; Faust, Saul N.; Finn, Adam; Flaxman, Amy L.; Hallis, Bassam; Heath, Paul; Jenkin, Daniel; Lazarus, Rajeka; Makinson, Rebecca; Minassian, Angela M.; Pollock, Katrina M.; Ramasamy, Maheshi; Robinson, Hannah; Snape, Matthew; Tarrant, Richard; Voysey, Merryn; Green, Catherine; Douglas, Alexander D.; Hill, Adrian V. S.; Lambe, Teresa; Gilbert, Sarah C.; Pollard, Andrew J.
    Lancet (2020), 396 (10249), 467-478CODEN: LANCAO; ISSN:0140-6736. (Elsevier Ltd.)
    The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) might be curtailed by vaccination. We assessed the safety, reactogenicity, and immunogenicity of a viral vectored coronavirus vaccine that expresses the spike protein of SARS-CoV-2. We did a phase 1/2, single-blind, randomised controlled trial in five trial sites in the UK of a chimpanzee adenovirus-vectored vaccine (ChAdOx1 nCoV-19) expressing the SARS-CoV-2 spike protein compared with a meningococcal conjugate vaccine (MenACWY) as control. Healthy adults aged 18-55 years with no history of lab. confirmed SARS-CoV-2 infection or of COVID-19-like symptoms were randomly assigned (1:1) to receive ChAdOx1 nCoV-19 at a dose of 5 x 1010 viral particles or MenACWY as a single i.m. injection. A protocol amendment in two of the five sites allowed prophylactic paracetamol to be administered before vaccination. Ten participants assigned to a non-randomised, unblinded ChAdOx1 nCoV-19 prime-boost group received a two-dose schedule, with the booster vaccine administered 28 days after the first dose. Humoral responses at baseline and following vaccination were assessed using a standardised total IgG ELISA against trimeric SARS-CoV-2 spike protein, a muliplexed immunoassay, three live SARS-CoV-2 neutralisation assays (a 50% plaque redn. neutralisation assay [PRNT50]; a microneutralisation assay [MNA50, MNA80, and MNA90]; and Marburg VN), and a pseudovirus neutralisation assay. Cellular responses were assessed using an ex-vivo interferon-γ enzyme-linked immunospot assay. The co-primary outcomes are to assess efficacy, as measured by cases of symptomatic virol. confirmed COVID-19, and safety, as measured by the occurrence of serious adverse events. Analyses were done by group allocation in participants who received the vaccine. Safety was assessed over 28 days after vaccination. Here, we report the preliminary findings on safety, reactogenicity, and cellular and humoral immune responses. The study is ongoing, and was registered at ISRCTN, 15281137, and ClinicalTrials.gov, NCT04324606. Between Apr. 23 and May 21, 2020, 1077 participants were enrolled and assigned to receive either ChAdOx1 nCoV-19 (n=543) or MenACWY (n=534), ten of whom were enrolled in the non-randomised ChAdOx1 nCoV-19 prime-boost group. Local and systemic reactions were more common in the ChAdOx1 nCoV-19 group and many were reduced by use of prophylactic paracetamol, including pain, feeling feverish, chills, muscle ache, headache, and malaise (all p<0·05). There were no serious adverse events related to ChAdOx1 nCoV-19. In the ChAdOx1 nCoV-19 group, spike-specific T-cell responses peaked on day 14 (median 856 spot-forming cells per million peripheral blood mononuclear cells, IQR 493-1802; n=43). Anti-spike IgG responses rose by day 28 (median 157 ELISA units [EU], 96-317; n=127), and were boosted following a second dose (639 EU, 360-792; n=10). Neutralising antibody responses against SARS-CoV-2 were detected in 32 (91%) of 35 participants after a single dose when measured in MNA80 and in 35 (100%) participants when measured in PRNT50. After a booster dose, all participants had neutralising activity (nine of nine in MNA80 at day 42 and ten of ten in Marburg VN on day 56). Neutralising antibody responses correlated strongly with antibody levels measured by ELISA (R2=0·67 by Marburg VN; p<0·001). ChAdOx1 nCoV-19 showed an acceptable safety profile, and homologous boosting increased antibody responses. These results, together with the induction of both humoral and cellular immune responses, support large-scale evaluation of this candidate vaccine in an ongoing phase 3 program.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhsVaku7fE&md5=4edd57b9d55d8a7c71ee84c8f62f7ca0
  24. 24
    Rouse, B. T.; Sehrawat, S. Immunity and Immunopathology to Viruses: What Decides the Outcome?. Nat. Rev. Immunol. 2010, 10, 514– 526,  DOI: 10.1038/nri2802
    Google Scholar
    24
    Immunity and immunopathology to viruses: what decides the outcome?
    Rouse, Barry T.; Sehrawat, Sharvan
    Nature Reviews Immunology (2010), 10 (7), 514-526CODEN: NRIABX; ISSN:1474-1733. (Nature Publishing Group)
    A review. Many viruses infect humans and most are controlled satisfactorily by the immune system with limited damage to host tissues. Some viruses, however, do cause overt damage to the host, either in isolated cases or as a reaction that commonly occurs after infection. The outcome is influenced by properties of the infecting virus, the circumstances of infection and several factors controlled by the host. In this Review, we focus on host factors that influence the outcome of viral infection, including genetic susceptibility, the age of the host when infected, the dose and route of infection, the induction of anti-inflammatory cells and proteins, as well as the presence of concurrent infections and past exposure to cross-reactive agents.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXnvFSgt78%253D&md5=a10d52b1ed35bea0d165b3cc88afd50b
  25. 25
    Klein, S. L.; Jedlicka, A.; Pekosz, A. The Xs and Y of Immune Responses to Viral Vaccines. Lancet Infect. Dis. 2010, 10, 338– 349,  DOI: 10.1016/S1473-3099(10)70049-9
    Google Scholar
    25
    The Xs and Y of immune responses to viral vaccines
    Klein, Sabra L.; Jedlicka, Anne; Pekosz, Andrew
    Lancet Infectious Diseases (2010), 10 (5), 338-349CODEN: LIDABP; ISSN:1473-3099. (Elsevier Ltd.)
    A review. Summary: The biol. differences assocd. with the sex of an individual are a major source of variation, affecting immune responses to vaccination. Compelling clin. data illustrate that men and women differ in their innate, humoral, and cell-mediated responses to viral vaccines. Sex affects the frequency and severity of adverse effects of vaccination, including fever, pain, and inflammation. Pregnancy can also substantially alter immune responses to vaccines. Data from clin. trials and animal models of vaccine efficacy lay the groundwork for future studies aimed at identifying the biol. mechanisms that underlie sex-specific responses to vaccines, including genetic and hormonal factors. An understanding and appreciation of the effect of sex and pregnancy on immune responses might change the strategies used by public health officials to start efficient vaccination programs (optimizing the timing and dose of the vaccine so that the max. no. of people are immunized), ensure sufficient levels of immune responses, minimize adverse effects, and allow for more efficient protection of populations that are high priority (eg, pregnant women and individuals with comorbid conditions).
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXht1WhsL7I&md5=581164b9d9113c651dc1901e737f6ffc
  26. 26
    Zhao, J.; Yuan, Q.; Wang, H.; Liu, W.; Liao, X.; Su, Y.; Wang, X.; Yuan, J.; Li, T.; Li, J.; Qian, S.; Hong, C.; Wang, F.; Liu, Y.; Wang, Z.; He, Q.; Li, Z.; He, B.; Zhang, T.; Fu, Y. Antibody Responses to SARS-CoV-2 in Patients of Novel Coronavirus Disease 2019. Clin. Infect. Dis. 2020,  DOI: 10.1093/cid/ciaa344
    Google Scholar
    There is no corresponding record for this reference.
  27. 27
    Chen, Z.; John Wherry, E. T Cell Responses in Patients with COVID-19. Nat. Rev. Immunol. 2020, 20, 529– 536,  DOI: 10.1038/s41577-020-0402-6
    Google Scholar
    27
    T cell responses in patients with COVID-19
    Chen, Zeyu; John Wherry, E.
    Nature Reviews Immunology (2020), 20 (9), 529-536CODEN: NRIABX; ISSN:1474-1733. (Nature Research)
    Abstr.: The role of T cells in the resoln. or exacerbation of COVID-19, as well as their potential to provide long-term protection from reinfection with SARS-CoV-2, remains debated. Nevertheless, recent studies have highlighted various aspects of T cell responses to SARS-CoV-2 infection that are starting to enable some general concepts to emerge.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhsVygtLvM&md5=2cf2f4b0bdf660e06e2574fbd505f32b
  28. 28
    Juno, J. A.; Tan, H.-X.; Lee, W. S.; Reynaldi, A.; Kelly, H. G.; Wragg, K.; Esterbauer, R.; Kent, H. E.; Batten, C. J.; Mordant, F. L.; Gherardin, N. A.; Pymm, P.; Dietrich, M. H.; Scott, N. E.; Tham, W.-H.; Godfrey, D. I.; Subbarao, K.; Davenport, M. P.; Kent, S. J.; Wheatley, A. K. Humoral and Circulating Follicular Helper T Cell Responses in Recovered Patients with COVID-19. Nat. Med. 2020, 26, 1428– 1434,  DOI: 10.1038/s41591-020-0995-0
    Google Scholar
    28
    Humoral and circulating follicular helper T cell responses in recovered patients with COVID-19
    Juno, Jennifer A.; Tan, Hyon-Xhi; Lee, Wen Shi; Reynaldi, Arnold; Kelly, Hannah G.; Wragg, Kathleen; Esterbauer, Robyn; Kent, Helen E.; Batten, C. Jane; Mordant, Francesca L.; Gherardin, Nicholas A.; Pymm, Phillip; Dietrich, Melanie H.; Scott, Nichollas E.; Tham, Wai-Hong; Godfrey, Dale I.; Subbarao, Kanta; Davenport, Miles P.; Kent, Stephen J.; Wheatley, Adam K.
    Nature Medicine (New York, NY, United States) (2020), 26 (9), 1428-1434CODEN: NAMEFI; ISSN:1078-8956. (Nature Research)
    Abstr.: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has dramatically expedited global vaccine development efforts1-3, most targeting the viral 'spike' glycoprotein (S). However, although prototypic S-based vaccines show promise in animal models12-14, the immunogenic properties of S in humans are poorly resolved. In this study, we characterized humoral and circulating follicular helper T cell (cTFH) immunity against spike in recovered patients with coronavirus disease 2019 (COVID-19). We found that S-specific antibodies, memory B cells and cTFH are consistently elicited after SARS-CoV-2 infection, demarking robust humoral immunity and pos. assocd. with plasma neutralizing activity. Comparatively low frequencies of B cells or cTFH specific for the receptor binding domain of S were elicited. Notably, the phenotype of S-specific cTFH differentiated subjects with potent neutralizing responses, providing a potential biomarker of potency for S-based vaccines entering the clinic. Overall, although patients who recovered from COVID-19 displayed multiple hallmarks of effective immune recognition of S, the wide spectrum of neutralizing activity obsd. suggests that vaccines might require strategies to selectively target the most potent neutralizing epitopes.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhtlynt7nE&md5=815451451dc3c9af0481599dd4f532ca
  29. 29
    Belongia, E. A.; Naleway, A. L. Smallpox Vaccine: The Good, the Bad, and the Ugly. Clin. Med. Res. 2003, 1, 87– 92,  DOI: 10.3121/cmr.1.2.87
    Google Scholar
    29
    Smallpox vaccine: the good, the bad, and the ugly
    Belongia Edward A; Naleway Allison L
    Clinical medicine & research (2003), 1 (2), 87-92 ISSN:1539-4182.
    Smallpox inarguably shaped the course of human history by killing countless millions in both the Old World and the New World. Dr. Edward Jenner's discovery of vaccination in the late 18th century, and the global eradication of smallpox in the 1970s, rank among the greatest achievements in human history. Amidst recent growing concerns about bioterrorism, smallpox vaccination has resurfaced from the history books to become a topic of major importance. Inoculation with vaccinia virus is highly effective for the prevention of smallpox infection, but it is associated with several known side effects that range from mild and self-limited to severe and life-threatening. As the United States moves forward with plans to vaccinate selected health care workers and the military, and perhaps offer the vaccination to all citizens in the future, it is important to fully understand and appreciate the history, risks, and benefits of smallpox vaccination.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BD2MritlKqug%253D%253D&md5=7e52639b593bb4c1a65d96186f3a8560
  30. 30
    Minor, P. D. An Introduction to Poliovirus: Pathogenesis, Vaccination, and the Endgame for Global Eradication. Methods Mol. Biol. 2016, 1387, 1– 10,  DOI: 10.1007/978-1-4939-3292-4_1
    Google Scholar
    30
    An introduction to poliovirus: pathogenesis, vaccination, and the endgame for global eradication
    Minor, Philip D.
    Methods in Molecular Biology (New York, NY, United States) (2016), 1387 (Poliovirus), 1-10CODEN: MMBIED; ISSN:1940-6029. (Springer)
    Poliomyelitis is caused by poliovirus, which is a pos. strand non-enveloped virus that occurs in three distinct serotypes (1, 2, and 3). Infection is mainly by the fecal-oral route and can be confi ned to the gut by antibodies induced either by vaccine, previous infection or maternally acquired. Vaccines include the live attenuated strains developed by Sabin and the inactivated vaccines developed by Salk; the live attenuated vaccine (Oral Polio Vaccine or OPV) has been the main tool in the Global Program of Polio eradication of the World Health Organization. Wild type 2 virus has not caused a case since 1999 and type 3 since 2012 and eradication seems near. However most infections are entirely silent so that sophisticated environmental surveillance may be needed to ensure that the virus has been eradicated, and the live vaccine can sometimes revert to virulent circulating forms under conditions that are not wholly understood. Cessation of vaccination is therefore an increasingly important issue and inactivated polio vaccine (IPV) is playing a larger part in the end game.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhs1yqsbvK&md5=bfd054dde95843357e97a98fa16f7871
  31. 31
    Gao, Y.; McKay, P. F.; Mann, J. F. S. Advances in HIV-1 Vaccine Development. Viruses 2018, 10, 167,  DOI: 10.3390/v10040167
    Google Scholar
    31
    Advances in HIV-1 vaccine development
    Gao, Yong; McKay, Paul F.; Mann, Jamie F. S.
    Viruses (2018), 10 (4), 167/1-167/26CODEN: VIRUBR; ISSN:1999-4915. (MDPI AG)
    A review. An efficacious HIV-1 vaccine is regarded as the best way to halt the ongoing HIV-1 epidemic. However, despite significant efforts to develop a safe and effective vaccine, the modestly protective RV144 trial remains the only efficacy trial to provide some level of protection against HIV-1 acquisition. This review will outline the history of HIV vaccine development, novel technologies being applied to HIV vaccinol. and immunogen design, as well as the studies that are ongoing to advance our understanding of vaccine-induced immune correlates of protection.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXisVWgtbnK&md5=c776907bb1c1afaa53e15409de8c1eaf
  32. 32
    Dudas, R. A.; Karron, R. A. Respiratory Syncytial Virus Vaccines. Clin. Microbiol. Rev. 1998, 11, 430– 439,  DOI: 10.1128/CMR.11.3.430
    Google Scholar
    32
    Respiratory syncytial virus vaccines
    Dudas R A; Karron R A
    Clinical microbiology reviews (1998), 11 (3), 430-9 ISSN:0893-8512.
    Respiratory syncytial virus (RSV) is the most important cause of viral lower respiratory tract illness (LRI) in infants and children worldwide and causes significant LRI in the elderly and in immunocompromised patients. The goal of RSV vaccination is to prevent serious RSV-associated LRI. There are several obstacles to the development of successful RSV vaccines, including the need to immunize very young infants, who may respond inadequately to vaccination; the existence of two antigenically distinct RSV groups, A and B; and the history of disease enhancement following administration of a formalin-inactivated vaccine. It is likely that more than one type of vaccine will be needed to prevent RSV LRI in the various populations at risk. Although vector delivery systems, synthetic peptide, and immune-stimulating complex vaccines have been evaluated in animal models, only the purified F protein (PFP) subunit vaccines and live attenuated vaccines have been evaluated in recent clinical trials. PFP-2 appears to be a promising vaccine for the elderly and for RSV-seropositive children with underlying pulmonary disease, whereas live cold-passaged (cp), temperature-sensitive (ts) RSV vaccines (denoted cpts vaccines) would most probably be useful in young infants. The availability of cDNA technology should allow further refinement of existing live attenuated cpts candidate vaccines to produce engineered vaccines that are satisfactorily attenuated, immunogenic, and phenotypically stable.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADyaK1czjtlKltA%253D%253D&md5=347f2f572c309e01d3e1c63e5cd80cd6
  33. 33
    Corthesy, B. Multi-Faceted Functions of Secretory IgA at Mucosal Surfaces. Front. Immunol. 2013,  DOI: 10.3389/fimmu.2013.00185
    Google Scholar
    There is no corresponding record for this reference.
  34. 34
    Chao, Y. X.; Rötzschke, O.; Tan, E.-K. The Role of IgA in COVID-19. Brain, Behav., Immun. 2020, 87, 182– 183,  DOI: 10.1016/j.bbi.2020.05.057
    Google Scholar
    34
    The role of IgA in COVID-19
    Chao, Yin Xia; Rotzschke, Olaf; Tan, Eng-King
    Brain, Behavior, and Immunity (2020), 87 (), 182-183CODEN: BBIMEW; ISSN:0889-1591. (Elsevier Inc.)
    Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 infection has affected close to 4 million people globally with more than 200,000 deaths and assocd. with various forms of morbidity and complications (Chan et al., 2020). The current virol. tests are either time consuming or of low sensitivity, which has serious implications on affected patients and general population. There is an urgent need for diagnostic tests so that effective treatment can be instituted. Secretory IgA plays a crucial role in the immune defense of mucosal surfaces, the first point of entry of SARS-CoV-2. IgA-based serol. tests targeting the SARS-CoV-2 specific Spike protein and nucleocapsid protein (NP) may thus represent an important diagnostic and therapeutic approach (Petherick, 2020; Okba et al., 2020).
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhtVels7vF&md5=f0bf38ea84bf54e7a092afa9ee73fccb
  35. 35
    Zhang, L.; Wang, W.; Wang, S. Effect of Vaccine Administration Modality on Immunogenicity and Efficacy. Expert Rev. Vaccines 2015, 14, 1509– 1523,  DOI: 10.1586/14760584.2015.1081067
    Google Scholar
    35
    Effect of vaccine administration modality on immunogenicity and efficacy
    Zhang, Lu; Wang, Wei; Wang, Shixia
    Expert Review of Vaccines (2015), 14 (11), 1509-1523CODEN: ERVXAX; ISSN:1476-0584. (Taylor & Francis Ltd.)
    The many factors impacting the efficacy of a vaccine can be broadly divided into three categories: features of the vaccine itself, including immunogen design, vaccine type, formulation, adjuvant and dosing; individual variations among vaccine recipients and vaccine administration-related parameters. While much literature exists related to vaccines, and recently systems biol. has started to dissect the impact of individual subject variation on vaccine efficacy, few studies have focused on the role of vaccine administration-related parameters on vaccine efficacy. Parenteral and mucosal vaccinations are traditional approaches for licensed vaccines; novel vaccine delivery approaches, including needless injection and adjuvant formulations, are being developed to further improve vaccine safety and efficacy. This review provides a brief summary of vaccine administration-related factors, including vaccination approach, delivery route and method of administration, to gain a better understanding of their potential impact on the safety and immunogenicity of candidate vaccines.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhslWgsL%252FN&md5=a293bb53c2f861b623d9f933f3124971
  36. 36
    Boyaka, P. N. Inducing Mucosal IgA: A Challenge for Vaccine Adjuvants and Delivery Systems. J. Immunol. 2017, 199, 9– 16,  DOI: 10.4049/jimmunol.1601775
    Google Scholar
    36
    Inducing Mucosal IgA: A Challenge for Vaccine Adjuvants and Delivery Systems
    Boyaka, Prosper N.
    Journal of Immunology (2017), 199 (1), 9-16CODEN: JOIMA3; ISSN:0022-1767. (American Association of Immunologists)
    Mucosal IgA or secretory IgA (SIgA) are structurally equipped to resist chem. degrdn. in the harsh environment of mucosal surfaces and enzymes of host or microbial origin. Prodn. of SIgA is finely regulated, and distinct T-independent and T-dependent mechanisms orchestrate Ig α class switching and SIgA responses against commensal and pathogenic microbes. Most infectious pathogens enter the host via mucosal surfaces. To provide a first line of protection at these entry ports, vaccines are being developed to induce pathogen-specific SIgA in addn. to systemic immunity achieved by injected vaccines. Mucosal or epicutaneous delivery of vaccines helps target the inductive sites for SIgA responses. The efficacy of such vaccines relies on the identification and/or engineering of vaccine adjuvants capable of supporting the development of SIgA alongside systemic immunity and delivery systems that improve vaccine delivery to the targeted anat. sites and immune cells.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhtVWmsb3N&md5=7b16d389486df37cdd7ca297e644649b
  37. 37
    Altimmune COVID-19 Vaccine Candidate Tested at UAB Shows Positive Preclinical Results - News. https://www.uab.edu/news/research/item/11426-altimmune-covid-19-vaccine-candidate-tested-at-uab-shows-positive-preclinical-results (accessed 2020-08-14).
    Google Scholar
    There is no corresponding record for this reference.
  38. 38
    OraPro-COVID-19. Home. https://www.stabilitech.com/orapro-covid-19/ (accessed 2020-08-14).
    Google Scholar
    There is no corresponding record for this reference.
  39. 39
    Quadram Researchers Working on COVID-19 Vaccine Join WHO Expert Groups. https://quadram.ac.uk/quadram-researchers-working-on-covid-19-vaccine-join-who-expert-groups/ (accessed Aug 14, 2020).
    Google Scholar
    There is no corresponding record for this reference.
  40. 40
    Zhang, Y.; Geng, X.; Tan, Y.; Li, Q.; Xu, C.; Xu, J.; Hao, L.; Zeng, Z.; Luo, X.; Liu, F.; Wang, H. New Understanding of the Damage of SARS-CoV-2 Infection Outside the Respiratory System. Biomed. Pharmacother. 2020, 127, 110195,  DOI: 10.1016/j.biopha.2020.110195
    Google Scholar
    40
    New understanding of the damage of SARS-CoV-2 infection outside the respiratory system
    Zhang, Yuhao; Geng, Xiuchao; Tan, Yanli; Li, Qiang; Xu, Can; Xu, Jianglong; Hao, Liangchao; Zeng, Zhaomu; Luo, Xianpu; Liu, Fulin; Wang, Hong
    Biomedicine & Pharmacotherapy (2020), 127 (), 110195CODEN: BIPHEX; ISSN:0753-3322. (Elsevier Masson SAS)
    A review. Since early Dec. 2019, a no. of pneumonia cases assocd. with unknown coronavirus infection were identified in Wuhan, China, and many addnl. cases were identified in other regions of China and in other countries within 3 mo. Currently, more than 80,000 cases have been diagnosed in China, including more than 3000 deaths. The epidemic is spreading to the rest of the world, posing a grave challenge to prevention and control. On Feb. 12, 2020, the International Committee on Taxonomy of Viruses and the World Health Organization officially named the novel coronavirus and assocd. pneumonia as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease 2019 (COVID-19), resp. According to the recent research on SARS-CoV-2, the virus mainly infects the respiratory system but may cause damage to other systems. In this paper, we will systematically review the pathogenic features, transmission routes, and infection mechanisms of SARS-CoV-2, as well as any adverse effects on the digestive system, urogenital system, central nervous system, and circulatory system, in order to provide a theor. and clin. basis for the diagnosis, classification, treatment, and prognosis assessment of SARS-CoV-2 infection.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXotlaqs7k%253D&md5=e32556c24767b83871721f5967ca2b17
  41. 41
    Kuba, K.; Imai, Y.; Penninger, J. M. Angiotensin-Converting Enzyme 2 in Lung Diseases. Curr. Opin. Pharmacol. 2006, 6, 271– 276,  DOI: 10.1016/j.coph.2006.03.001
    Google Scholar
    41
    Angiotensin-converting enzyme 2 in lung diseases
    Kuba, Keiji; Imai, Yumiko; Penninger, Josef M.
    Current Opinion in Pharmacology (2006), 6 (3), 271-276CODEN: COPUBK; ISSN:1471-4892. (Elsevier Ltd.)
    A review. The renin-angiotensin system (RAS) plays a key role in maintaining blood pressure homeostasis, as well as fluid and salt balance. Angiotensin II, a key effector peptide of the system, causes vasoconstriction and exerts multiple biol. functions. Angiotensin-converting enzyme (ACE) plays a central role in generating angiotensin II from angiotensin I, and capillary blood vessels in the lung are one of the major sites of ACE expression and angiotensin II prodn. in the human body. The RAS has been implicated in the pathogenesis of pulmonary hypertension and pulmonary fibrosis, both commonly seen in chronic lung diseases such as chronic obstructive lung disease. Recent studies indicate that the RAS also plays a crit. role in acute lung diseases, esp. acute respiratory distress syndrome (ARDS). ACE2, a close homolog of ACE, functions as a neg. regulator of the angiotensin system and was identified as a key receptor for SARS (severe acute respiratory syndrome) coronavirus infections. In the lung, ACE2 protects against acute lung injury in several animal models of ARDS. Thus, the RAS appears to play a crit. role in the pathogenesis of acute lung injury. Indeed, increasing ACE2 activity might be a novel approach for the treatment of acute lung failure in several diseases.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD28XksFynu7c%253D&md5=ee10aae36a7af1b675149f411db37d72
  42. 42
    Xia, H.; Lazartigues, E. Angiotensin-converting Enzyme 2 in the Brain: Properties and Future Directions. J. Neurochem. 2008, 107, 1482– 1494,  DOI: 10.1111/j.1471-4159.2008.05723.x
    Google Scholar
    42
    Angiotensin-converting enzyme 2 in the brain: properties and future directions
    Xia, Huijing; Lazartigues, Eric
    Journal of Neurochemistry (2008), 107 (6), 1482-1494CODEN: JONRA9; ISSN:0022-3042. (Wiley-Blackwell)
    A review. Angiotensin (Ang)-converting enzyme (ACE) 2 cleaves Ang-II into the vasodilator peptide Ang-(1-7), thus acting as a pivotal element in balancing the local effects of these peptides. ACE2 has been identified in various tissues and is supposed to be a modulator of cardiovascular function. Decreases in ACE2 expression and activity have been reported in models of hypertension, heart failure, atherosclerosis, diabetic nephropathy and others. In addn., the expression level and/or activity are affected by other renin-angiotensin system components (e.g., ACE and AT1 receptors). Local inhibition or global deletion of brain ACE2 induces a redn. in baroreflex sensitivity. Moreover, ACE2-null mice have been shown to exhibit either blood pressure or cardiac dysfunction phenotypes. On the other hand, over-expression of ACE2 exerts protective effects in local tissues, including the brain. In this review, we will first summarize the major findings linking ACE2 to cardiovascular function in the periphery then focus on recent discoveries related to ACE2 in the CNS. Finally, we will unveil new tools designed to address the importance of central ACE2 in various diseases, and discuss the potential for this carboxypeptidase as a new target in the treatment of hypertension and other cardiovascular diseases.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXis1Sksg%253D%253D&md5=b497b1111e6aac23f5d992a5548a65b6
  43. 43
    Wang, J.; Zhao, S.; Liu, M.; Zhao, Z.; Xu, Y.; Wang, P.; Lin, M.; Xu, Y.; Huang, B.; Zuo, X.; Chen, Z.; Bai, F.; Cui, J.; Lew, A. M.; Zhao, J.; Zhang, Y.; Luo, H.; Zhang, Y. ACE2 Expression by Colonic Epithelial Cells Is Associated with Viral Infection, Immunity and Energy Metabolism. medRxiv 2020, 2020.02.05.20020545. https://www.medrxiv.org/content/10.1101/2020.02.05.20020545v1 (accessed 2020-08-06).
    Google Scholar
    There is no corresponding record for this reference.
  44. 44
    Charles A Janeway, J.; Travers, P.; Walport, M.; Shlomchik, M. J. The Distribution and Functions of Immunoglobulin Isotypes. Immunobiology: The Immune System in Health and Disease, 5; Garland Science: New York, 2001.
    Google Scholar
    There is no corresponding record for this reference.
  45. 45
    Gilbert, S. C. T-Cell-Inducing Vaccines – What’s the Future. Immunology 2012, 135, 19– 26,  DOI: 10.1111/j.1365-2567.2011.03517.x
    Google Scholar
    45
    T-cell-inducing vaccines - what's the future
    Gilbert, Sarah C.
    Immunology (2012), 135 (1), 19-26CODEN: IMMUAM; ISSN:0019-2805. (Wiley-Blackwell)
    A review. In the twentieth century vaccine development has moved from the use of attenuated or killed micro-organisms to protein sub-unit vaccines, with vaccine immunogenicity assessed by measuring antibodies induced by vaccination. However, for many infectious diseases T cells are an important part of naturally acquired protective immune responses, and inducing these by vaccination has been the aim of much research. The progress that has been made in developing effective T-cell-inducing vaccines against viral and parasitic diseases such as HIV and malaria is discussed, along with recent developments in therapeutic vaccine development for chronic viral infections and cancer. Although many ways of inducing T cells by vaccination have been assessed, the majority result in low level, non-protective responses. Sufficient clin. research has now been conducted to establish that replication-deficient viral vectored vaccines lead the field in inducing strong and broad responses, and efficacy studies of T-cell-inducing vaccines against a no. of diseases are finally demonstrating that this is a valid approach to filling the gaps in our defense against not only infectious disease, but some forms of cancer.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXhs12ntLzO&md5=ea972d5f9096b5d53dcc6931f58b74ae
  46. 46
    Todryk, S. M. T Cell Memory to Vaccination. Vaccines (Basel, Switz.) 2018, 6, 84,  DOI: 10.3390/vaccines6040084
    Google Scholar
    46
    T cell memory to vaccination
    Todryk, Stephen M.
    Vaccines (Basel, Switzerland) (2018), 6 (4), 84CODEN: VBSABP; ISSN:2076-393X. (MDPI AG)
    Most immune responses assocd. with vaccination are controlled by specific T cells of a CD4+ helper phenotype which mediate the generation of effector antibodies, cytotoxic T lymphocytes (CTLs), or the activation of innate immune effector cells. A rapidly growing understanding of the generation, maintenance, activity, and measurement of such T cells is leading to vaccination strategies with greater efficacy and potentially greater microbial coverage.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXktFyitLo%253D&md5=d9f50554bedadd53188e891278bd91d7
  47. 47
    Lange, H.; Hecht, O.; Zemlin, M.; Trad, A.; Tanasa, R. I.; Schroeder, H. W.; Lemke, H. Immunoglobulin Class Switching Appears to Be Regulated by B Cell Antigen Receptor-Specific T Cell Action. Eur. J. Immunol. 2012, 42, 1016– 1029,  DOI: 10.1002/eji.201141857
    Google Scholar
    47
    Immunoglobulin class switching appears to be regulated by B-cell antigen receptor-specific T-cell action
    Lange, Hans; Hecht, Oliver; Zemlin, Michael; Trad, Ahmad; Tanasa, Radu I.; Schroeder, Harry W.; Lemke, Hilmar
    European Journal of Immunology (2012), 42 (4), 1016-1029CODEN: EJIMAF; ISSN:0014-2980. (Wiley-VCH Verlag GmbH & Co. KGaA)
    Antigen affinity is commonly viewed as the driving force behind the selection for dominant clonotypes that can occur during the T-cell-dependent processes of class switch recombination (CSR) and immune maturation. To test this view, we analyzed the variable gene repertoires of natural monoclonal antibodies to the hapten 2-phenyloxazolone (phOx) as well as those generated after phOx protein carrier-induced thymus-dependent or Ficoll-induced thymus-independent antigen stimulation. In contrast to expectations, the extent of IgM heterogeneity proved similar and many IgM from these three populations exhibited similar or even greater affinities than the classic Ox1 clonotype that dominates only after CSR among primary and memory IgG. The population of clones that were selected during CSR exhibited a reduced VH/VL repertoire that was enriched for variable domains with shorter and more uniform CDR-H3 lengths and almost completely stripped of variable domains encoded by the large VH1 family. Thus, contrary to the current paradigm, T-cell-dependent clonal selection during CSR appeared to select for VH family and CDR-H3 loop content even when the affinity provided by alternative clones exhibited similar to increased affinity for antigen.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XmtVKrtL8%253D&md5=18f6f00ff3f75581637e645e026dd4f6
  48. 48
    Lin, Q.; Zhu, L.; Ni, Z.; Meng, H.; You, L. Duration of Serum Neutralizing Antibodies for SARS-CoV-2: Lessons from SARS-CoV Infection. J. Microbiol., Immunol. Infect. 2020, 53, 821,  DOI: 10.1016/j.jmii.2020.03.015
    Google Scholar
    48
    Duration of serum neutralizing antibodies for SARS-CoV-2: Lessons from SARS-CoV infection
    Lin, Qingqing; Zhu, Li; Ni, Zuowei; Meng, Haitao; You, Liangshun
    Journal of Microbiology, Immunology and Infection (2020), 53 (5), 821-822CODEN: JMIIFG; ISSN:1995-9133. (Elsevier Taiwan LLC)
    The authors examine the reports of protection afforded by specific antibodies in convalescent SARS-CoV patients. The finding suggested that the immune responses of specific Abs were maintained in more than 90% of recovered SARS-CoV patients for 2 years.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXlvFyrtb4%253D&md5=70eaa8a770a0674ba8fe02a9398a59e0
  49. 49
    Clinical Stage Pipeline – Novavax – Creating Tomorrow’s Vaccines Today. Novavax.com. https://novavax.com/our-pipeline#nvx-cov2373 (accessed 2020-08-14).
    Google Scholar
    There is no corresponding record for this reference.
  50. 50
    Coffman, R. L.; Sher, A.; Seder, R. A. Vaccine Adjuvants: Putting Innate Immunity to Work. Immunity 2010, 33, 492– 503,  DOI: 10.1016/j.immuni.2010.10.002
    Google Scholar
    50
    Vaccine Adjuvants: Putting Innate Immunity to Work
    Coffman, Robert L.; Sher, Alan; Seder, Robert A.
    Immunity (2010), 33 (4), 492-503CODEN: IUNIEH; ISSN:1074-7613. (Cell Press)
    A review. Adjuvants enhance immunity to vaccines and exptl. antigens by a variety of mechanisms. In the past decade, many receptors and signaling pathways in the innate immune system have been defined and these innate responses strongly influence the adaptive immune response. The focus of this review is to delineate the innate mechanisms by which adjuvants mediate their effects. We highlight how adjuvants can be used to influence the magnitude and alter the quality of the adaptive response in order to provide max. protection against specific pathogens. Despite the impressive success of currently approved adjuvants for generating immunity to viral and bacterial infections, there remains a need for improved adjuvants that enhance protective antibody responses, esp. in populations that respond poorly to current vaccines. However, the larger challenge is to develop vaccines that generate strong T cell immunity with purified or recombinant vaccine antigens.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXhtlGmtLvF&md5=26e53f025adef76f6446093b935c52b3
  51. 51
    McKee, A. S.; MacLeod, M. K. L.; Kappler, J. W.; Marrack, P. Immune Mechanisms of Protection: Can Adjuvants Rise to the Challenge?. BMC Biol. 2010, 8, 37,  DOI: 10.1186/1741-7007-8-37
    Google Scholar
    51
    Immune mechanisms of protection: can adjuvants rise to the challenge?
    McKee Amy S; MacLeod Megan K L; Kappler John W; Marrack Philippa
    BMC biology (2010), 8 (), 37 ISSN:.
    For many diseases vaccines are lacking or only partly effective. Research on protective immunity and adjuvants that generate vigorous immune responses may help generate effective vaccines against such pathogens.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC3c3lsFGrsg%253D%253D&md5=5e16bce0994434d63890142ac358e987
  52. 52
    Kreutz, M.; Giquel, B.; Hu, Q.; Abuknesha, R.; Uematsu, S.; Akira, S.; Nestle, F. O.; Diebold, S. S. Antibody-Antigen-Adjuvant Conjugates Enable Co-Delivery of Antigen and Adjuvant to Dendritic Cells in Cis but Only Have Partial Targeting Specificity. PLoS One 2012, 7, e40208  DOI: 10.1371/journal.pone.0040208
    Google Scholar
    52
    Antibody-antigen-adjuvant conjugates enable co-delivery of antigen and adjuvant to dendritic cells in cis but only have partial targeting specificity
    Kreutz, Martin; Giquel, Benoit; Hu, Qin; Abuknesha, Ram; Uematsu, Satoshi; Akira, Shizuo; Nestle, Frank O.; Diebold, Sandra S.
    PLoS One (2012), 7 (7), e40208CODEN: POLNCL; ISSN:1932-6203. (Public Library of Science)
    Antibody-antigen conjugates, which promote antigen-presentation by dendritic cells (DC) by means of targeted delivery of antigen to particular DC subsets, represent a powerful vaccination approach. To ensure immunity rather than tolerance induction the co-administration of a suitable adjuvant is paramount. However, co-administration of unlinked adjuvant cannot ensure that all cells targeted by the antibody conjugates are appropriately activated. Furthermore, antigen-presenting cells (APC) that do not present the desired antigen are equally strongly activated and could prime undesired responses against self-antigens. We, therefore, were interested in exploring targeted co-delivery of antigen and adjuvant in cis in form of antibody-antigen-adjuvant conjugates for the induction of anti-tumor immunity. In this study, we report on the assembly and characterization of conjugates consisting of DEC205-specific antibody, the model antigen ovalbumin (OVA) and CpG oligodeoxynucleotides (ODN). We show that such conjugates are more potent at inducing cytotoxic T lymphocyte (CTL) responses than control conjugates mixed with sol. CpG. However, our study also reveals that the nucleic acid moiety of such antibody-antigen-adjuvant conjugates alters their binding and uptake and allows delivery of the antigen and the adjuvant to cells partially independently of DEC205. Nevertheless, antibody-antigen-adjuvant conjugates are superior to antibody-free antigen-adjuvant conjugates in priming CTL responses and efficiently induce anti-tumor immunity in the murine B16 pseudo-metastasis model. A better understanding of the role of the antibody moiety is required to inform future conjugate vaccination strategies for efficient induction of anti-tumor responses.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhtVGmtrfM&md5=142120e1e276f1600da9d5b018759397
  53. 53
    Wang, Z.-B.; Xu, J. Better Adjuvants for Better Vaccines: Progress in Adjuvant Delivery Systems, Modifications, and Adjuvant–Antigen Codelivery. Vaccines (Basel, Switz.) 2020, 8, 128,  DOI: 10.3390/vaccines8010128
    Google Scholar
    53
    Better adjuvants for better vaccines: progress in adjuvant delivery systems, modifications, and adjuvant-antigen codelivery
    Wang, Zhi-Biao; Xu, Jing
    Vaccines (Basel, Switzerland) (2020), 8 (1), 128CODEN: VBSABP; ISSN:2076-393X. (MDPI AG)
    Traditional aluminum adjuvants can trigger strong humoral immunity but weak cellular immunity, limiting their application in some vaccines. Currently, various immunomodulators and delivery carriers are used as adjuvants, and the mechanisms of action of some of these adjuvants are clear. However, customizing targets of adjuvant action (cellular or humoral immunity) and action intensity (enhancement or inhibition) according to different antigens selected is time-consuming. Here, we review the adjuvant effects of some delivery systems and immune stimulants. In addn., to improve the safety, effectiveness, and accessibility of adjuvants, new trends in adjuvant development and their modification strategies are discussed.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhsVChsLjN&md5=a95c03fb6a20afd40a3b2695738b6ac1
  54. 54
    Pati, R.; Shevtsov, M.; Sonawane, A. Nanoparticle Vaccines against Infectious Diseases. Front. Immunol. 2018,  DOI: 10.3389/fimmu.2018.02224
    Google Scholar
    There is no corresponding record for this reference.
  55. 55
    Chattopadhyay, S.; Chen, J.-Y.; Chen, H.-W.; Hu, C.-M. J. Nanoparticle Vaccines Adopting Virus-Like Features for Enhanced Immune Potentiation. Nanotheranostics 2017, 1, 244– 260,  DOI: 10.7150/ntno.19796
    Google Scholar
    55
    Nanoparticle Vaccines Adopting Virus-like Features for Enhanced Immune Potentiation
    Chattopadhyay Saborni; Chen Jui-Yi; Hu Che-Ming Jack; Chattopadhyay Saborni; Chen Hui-Wen; Chen Hui-Wen; Hu Che-Ming Jack
    Nanotheranostics (2017), 1 (3), 244-260 ISSN:.
    Synthetic nanoparticles play an increasingly significant role in vaccine design and development as many nanoparticle vaccines show improved safety and efficacy over conventional formulations. These nanoformulations are structurally similar to viruses, which are nanoscale pathogenic organisms that have served as a key selective pressure driving the evolution of our immune system. As a result, mechanisms behind the benefits of nanoparticle vaccines can often find analogue to the interaction dynamics between the immune system and viruses. This review covers the advances in vaccine nanotechnology with a perspective on the advantages of virus mimicry towards immune potentiation. It provides an overview to the different types of nanomaterials utilized for nanoparticle vaccine development, including functionalization strategies that bestow nanoparticles with virus-like features. As understanding of human immunity and vaccine mechanisms continue to evolve, recognizing the fundamental semblance between synthetic nanoparticles and viruses may offer an explanation for the superiority of nanoparticle vaccines over conventional vaccines and may spur new design rationales for future vaccine research. These nanoformulations are poised to provide solutions towards pressing and emerging human diseases.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC1M7ks1SgsA%253D%253D&md5=b2fc2f2c624f586c8bd909a64a00501d
  56. 56
    Wrapp, D.; Wang, N.; Corbett, K. S.; Goldsmith, J. A.; Hsieh, C.-L.; Abiona, O.; Graham, B. S.; McLellan, J. S. Cryo-EM Structure of the 2019-NCoV Spike in the Prefusion Conformation. Science 2020, 367, 1260– 1263,  DOI: 10.1126/science.abb2507
    Google Scholar
    56
    Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation
    Wrapp, Daniel; Wang, Nianshuang; Corbett, Kizzmekia S.; Goldsmith, Jory A.; Hsieh, Ching-Lin; Abiona, Olubukola; Graham, Barney S.; McLellan, Jason S.
    Science (Washington, DC, United States) (2020), 367 (6483), 1260-1263CODEN: SCIEAS; ISSN:1095-9203. (American Association for the Advancement of Science)
    The outbreak of a novel coronavirus (2019-nCoV) represents a pandemic threat that has been declared a public health emergency of international concern. The CoV spike (S) glycoprotein is a key target for vaccines, therapeutic antibodies, and diagnostics. To facilitate medical countermeasure development, we detd. a 3.5-angstrom-resoln. cryo-electron microscopy structure of the 2019-nCoV S trimer in the prefusion conformation. The predominant state of the trimer has one of the three receptor-binding domains (RBDs) rotated up in a receptor-accessible conformation. We also provide biophys. and structural evidence that the 2019-nCoV S protein binds angiotensin-converting enzyme 2 (ACE2) with higher affinity than does severe acute respiratory syndrome (SARS)-CoV S. Addnl., we tested several published SARS-CoV RBD-specific monoclonal antibodies and found that they do not have appreciable binding to 2019-nCoV S, suggesting that antibody cross-reactivity may be limited between the two RBDs. The structure of 2019-nCoV S should enable the rapid development and evaluation of medical countermeasures to address the ongoing public health crisis.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXkvFemt70%253D&md5=27d08cbb9a43d1da051a8a92a9f68aa5
  57. 57
    Kanekiyo, M.; Joyce, M. G.; Gillespie, R. A.; Gallagher, J. R.; Andrews, S. F.; Yassine, H. M.; Wheatley, A. K.; Fisher, B. E.; Ambrozak, D. R.; Creanga, A.; Leung, K.; Yang, E. S.; Boyoglu-Barnum, S.; Georgiev, I. S.; Tsybovsky, Y.; Prabhakaran, M. S.; Andersen, H.; Kong, W.-P.; Baxa, U.; Zephir, K. L. Mosaic Nanoparticle Display of Diverse Influenza Virus Hemagglutinins Elicits Broad B Cell Responses. Nat. Immunol. 2019, 20, 362– 372,  DOI: 10.1038/s41590-018-0305-x
    Google Scholar
    57
    Mosaic nanoparticle display of diverse influenza virus hemagglutinins elicits broad B cell responses
    Kanekiyo, Masaru; Joyce, M. Gordon; Gillespie, Rebecca A.; Gallagher, John R.; Andrews, Sarah F.; Yassine, Hadi M.; Wheatley, Adam K.; Fisher, Brian E.; Ambrozak, David R.; Creanga, Adrian; Leung, Kwanyee; Yang, Eun Sung; Boyoglu-Barnum, Seyhan; Georgiev, Ivelin S.; Tsybovsky, Yaroslav; Prabhakaran, Madhu S.; Andersen, Hanne; Kong, Wing-Pui; Baxa, Ulrich; Zephir, Kathryn L.; Ledgerwood, Julie E.; Koup, Richard A.; Kwong, Peter D.; Harris, Audray K.; McDermott, Adrian B.; Mascola, John R.; Graham, Barney S.
    Nature Immunology (2019), 20 (3), 362-372CODEN: NIAMCZ; ISSN:1529-2908. (Nature Research)
    The present vaccine against influenza virus has the inevitable risk of antigenic discordance between the vaccine and the circulating strains, which diminishes vaccine efficacy. This necessitates new approaches that provide broader protection against influenza. Here we designed a vaccine using the hypervariable receptor-binding domain (RBD) of viral hemagglutinin displayed on a nanoparticle (np) able to elicit antibody responses that neutralize H1N1 influenza viruses spanning over 90 years. Co-display of RBDs from multiple strains across time, so that the adjacent RBDs are heterotypic, provides an avidity advantage to cross-reactive B cells. Immunization with the mosaic RBD-np elicited broader antibody responses than those induced by an admixt. of nanoparticles encompassing the same set of RBDs as sep. homotypic arrays. Furthermore, we identified a broadly neutralizing monoclonal antibody in a mouse immunized with mosaic RBD-np. The mosaic antigen array signifies a unique approach that subverts monotypic immunodominance and allows otherwise subdominant cross-reactive B cell responses to emerge.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXmtFKktrw%253D&md5=ac54fd5220413d1d6d478228830b4d1c
  58. 58
    Cueni, L. N.; Detmar, M. The Lymphatic System in Health and Disease. Lymphatic Res. Biol. 2008, 6, 109– 122,  DOI: 10.1089/lrb.2008.1008
    Google Scholar
    58
    The lymphatic system in health and disease
    Cueni Leah N; Detmar Michael
    Lymphatic research and biology (2008), 6 (3-4), 109-22 ISSN:1539-6851.
    The lymphatic vascular system has an important role in the regulation of tissue pressure, immune surveillance and the absorption of dietary fat in the intestine. There is growing evidence that the lymphatic system also contributes to a number of diseases, such as lymphedema, cancer metastasis and different inflammatory disorders. The discovery of various molecular markers allowing the distinction of blood and lymphatic vessels, together with the availability of a increasing number of in vitro and in vivo models to study various aspects of lymphatic biology, has enabled tremendous progress in research into the development and function of the lymphatic system. This review discusses recent advances in our understanding of the embryonic development of the lymphatic vasculature, the molecular mechanisms mediating lymphangiogenesis in the adult, the role of lymphangiogenesis in chronic inflammation and lymphatic cancer metastasis, and the emerging importance of the lymphatic vasculature as a therapeutic target.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BD1M%252FjvFKksA%253D%253D&md5=8fd29107de0b47951255215a40ec5054
  59. 59
    Cai, S.; Zhang, Q.; Bagby, T.; Forrest, M. L. Lymphatic Drug Delivery Using Engineered Liposomes and Solid Lipid Nanoparticles. Adv. Drug Delivery Rev. 2011, 63, 901– 908,  DOI: 10.1016/j.addr.2011.05.017
    Google Scholar
    59
    Lymphatic drug delivery using engineered liposomes and solid lipid nanoparticles
    Cai, Shuang; Yang, Qiuhong; Bagby, Taryn R.; Forrest, M. Laird
    Advanced Drug Delivery Reviews (2011), 63 (10-11), 901-908CODEN: ADDREP; ISSN:0169-409X. (Elsevier B.V.)
    A review. The lymphatic system plays a crucial role in the immune system's recognition and response to disease, and most solid cancers initially spread from the primary site via the tumor's surrounding lymphatics before hematol. dissemination. Hence, the lymphatic system is an important target for developing new vaccines, cancer treatments, and diagnostic agents. Targeting the lymphatic system by s.c., intestinal, and pulmonary routes was evaluated and subsequently utilized to improve lymphatic penetration and retention of drug mols., reduce drug-related systemic toxicities, and enhance bioavailability of poorly sol. and unstable drugs. Lymphatic imaging is an essential tool for the detection and staging of cancer. New nano-based technologies offer improved detection and characterization of the nodal diseases, while new delivery devices can better target and confine treatments to tumors within the nodal space while sparing healthy tissues. This manuscript reviews recent advances in the field of lymphatic drug delivery and imaging and focuses specifically on the development of liposomes and solid lipid nanoparticles for lymphatic introduction via the s.c., intestinal, and pulmonary routes.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXhtV2ntbjM&md5=17ebde4cabf30b63e36e8333025d2823
  60. 60
    eTheRNA Launches an International Consortium and Starts Development of Cross-Strain Protective CoV-2 mRNA Vaccine for High Risk Populations. https://finance.yahoo.com/news/etherna-launches-international-consortium-starts-080000668.html (accessed 2020-09-16).
    Google Scholar
    There is no corresponding record for this reference.
  61. 61
    B.V, I. Intravacc Partners with Wageningen Bioveterinary Research and Utrecht University to Develop an Intranasal COVID-19 Vaccine. https://www.prnewswire.com/news-releases/intravacc-partners-with-wageningen-bioveterinary-research-and-utrecht-university-to-develop-an-intranasal-covid-19-vaccine-301070721.html (accessed 2020-09-16).
    Google Scholar
    There is no corresponding record for this reference.
  62. 62
    Shin, M. D.; Shukla, S.; Chung, Y. H.; Beiss, V.; Chan, S. K.; Ortega-Rivera, O. A.; Wirth, D. M.; Chen, A.; Sack, M.; Pokorski, J. K.; Steinmetz, N. F. COVID-19 Vaccine Development and a Potential Nanomaterial Path Forward. Nat. Nanotechnol. 2020, 15, 646– 655,  DOI: 10.1038/s41565-020-0737-y
    Google Scholar
    62
    COVID-19 vaccine development and a potential nanomaterial path forward
    Shin, Matthew D.; Shukla, Sourabh; Chung, Young Hun; Beiss, Veronique; Chan, Soo Khim; Ortega-Rivera, Oscar A.; Wirth, David M.; Chen, Angela; Sack, Markus; Pokorski, Jonathan K.; Steinmetz, Nicole F.
    Nature Nanotechnology (2020), 15 (8), 646-655CODEN: NNAABX; ISSN:1748-3387. (Nature Research)
    A review. Abstr.: The COVID-19 pandemic has infected millions of people with no clear signs of abatement owing to the high prevalence, long incubation period and lack of established treatments or vaccines. Vaccines are the most promising soln. to mitigate new viral strains. The genome sequence and protein structure of the 2019-novel coronavirus (nCoV or SARS-CoV-2) were made available in record time, allowing the development of inactivated or attenuated viral vaccines along with subunit vaccines for prophylaxis and treatment. Nanotechnol. benefits modern vaccine design since nanomaterials are ideal for antigen delivery, as adjuvants, and as mimics of viral structures. In fact, the first vaccine candidate launched into clin. trials is an mRNA vaccine delivered via lipid nanoparticles. To eradicate pandemics, present and future, a successful vaccine platform must enable rapid discovery, scalable manufg. and global distribution. Here, we review current approaches to COVID-19 vaccine development and highlight the role of nanotechnol. and advanced manufg.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhsVSju73L&md5=7e381a11e739e763f63bd0ff3e5c3a07
  63. 63
    Milken Institute’s COVID-19 Treatment and Vaccine Tracker Tracks the Development of Treatments and Vaccines for COVID-19. https://covid-19tracker.milkeninstitute.org/ (accessed 2020-08-03).
    Google Scholar
    There is no corresponding record for this reference.
  64. 64
    Delrue, I.; Verzele, D.; Madder, A.; Nauwynck, H. J. Inactivated Virus Vaccines from Chemistry to Prophylaxis: Merits, Risks and Challenges. Expert Rev. Vaccines 2012, 11, 695– 719,  DOI: 10.1586/erv.12.38
    Google Scholar
    64
    Inactivated virus vaccines from chemistry to prophylaxis: merits, risks and challenges
    Delrue, Iris; Verzele, Dieter; Madder, Annemieke; Nauwynck, Hans J.
    Expert Review of Vaccines (2012), 11 (6), 695-719CODEN: ERVXAX; ISSN:1476-0584. (Expert Reviews Ltd.)
    The aim of this review is to make researchers aware of the benefits of an efficient quality control system for prediction of a developed vaccine's efficacy. Two major goals should be addressed when inactivating a virus for vaccine purposes: first, the infectious virus should be inactivated completely in order to be safe, and second, the viral epitopes important for the induction of protective immunity should be conserved after inactivation in order to have an antigen of high quality. Therefore, some problems assocd. with the virus inactivation process, such as virus aggregate formation, protein crosslinking, protein denaturation and degrdn. should be addressed before testing an inactivated vaccine in vivo.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhtFKjurrN&md5=7b3125e1681156508660c1b6e9cb014f
  65. 65
    Pulendran, B.; Ahmed, R. Immunological Mechanisms of Vaccination. Nat. Immunol. 2011, 12, 509– 517,  DOI: 10.1038/ni.2039
    Google Scholar
    65
    Immunological mechanisms of vaccination
    Pulendran, Bali; Ahmed, Rafi
    Nature Immunology (2011), 12 (6), 509-517CODEN: NIAMCZ; ISSN:1529-2908. (Nature Publishing Group)
    A review. Vaccines represent one of the greatest triumphs of modern medicine. Despite the common origins of vaccinol. and immunol. more than 200 years ago, the two disciplines have evolved along such different trajectories that most of the highly successful vaccines have been made empirically, with little or no immunol. insight. Recent advances in innate immunity have offered new insights about the mechanisms of vaccine-induced immunity and have facilitated a more rational approach to vaccine design. Here we will discuss these advances and emerging themes on the immunol. of vaccination.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXmtF2lu7o%253D&md5=09eeeb323fd6c819c4939eaf7cb69761
  66. 66
    Vartak, A.; Sucheck, S. J. Recent Advances in Subunit Vaccine Carriers. Vaccines (Basel, Switz.) 2016, 4, 12,  DOI: 10.3390/vaccines4020012
    Google Scholar
    66
    Recent advances in subunit vaccine carriers
    Vartak, Abhishek; Sucheck, Steven J.
    Vaccines (Basel, Switzerland) (2016), 4 (2), 12/1-12/18CODEN: VBSABP; ISSN:2076-393X. (MDPI AG)
    The lower immunogenicity of synthetic subunit antigens, compared to live attenuated vaccines, is being addressed with improved vaccine carriers. Recent reports indicate that the physio-chem. properties of these carriers can be altered to achieve optimal antigen presentation, endosomal escape, particle bio-distribution, and cellular trafficking. The carriers can be modified with various antigens and ligands for dendritic cells targeting. They can also be modified with adjuvants, either covalently or entrapped in the matrix, to improve cellular and humoral immune responses against the antigen. As a result, these multi-functional carrier systems are being explored for use in active immunotherapy against cancer and infectious diseases. Advancing technol., improved anal. methods, and use of computational methodol. have also contributed to the development of subunit vaccine carriers. This review details recent breakthroughs in the design of nano-particulate vaccine carriers, including liposomes, polymeric nanoparticles, and inorg. nanoparticles.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXnvF2mtbg%253D&md5=16f5079047f303f38533eca9e0e2e653
  67. 67
    Vogel, F. R.; Sarver, N. Nucleic Acid Vaccines. Clin. Microbiol. Rev. 1995, 8, 406– 410,  DOI: 10.1128/CMR.8.3.406
    Google Scholar
    67
    Nucleic acid vaccines
    Vogel, Frederick R.; Sarver, Nava
    Clinical Microbiology Reviews (1995), 8 (3), 406-10CODEN: CMIREX; ISSN:0893-8512. (American Society for Microbiology)
    A review, with 32 refs. The authors discuss nucleic acid vaccines development, DNA vaccines against retroviruses, retrovirus-mediated gene transfer, parameters affecting gene expression and immunogenicity of DNA vaccines, safety considerations for nucleic acid vaccines, and RNA vaccines.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2MXnt1OqsLg%253D&md5=ae1b5593aa383168bf3df775fcfcae3a
  68. 68
    Choi, Y.; Chang, J. Viral Vectors for Vaccine Applications. Clin. Exp. Vaccine Res. 2013, 2, 97– 105,  DOI: 10.7774/cevr.2013.2.2.97
    Google Scholar
    68
    Viral vectors for vaccine applications
    Choi, Youngjoo; Chang, Jun
    Clinical and Experimental Vaccine Research (2013), 2 (2), 97-105CODEN: CEVRA4; ISSN:2287-3651. (Korean Vaccine Society)
    A review. Traditional approach of inactivated or live-attenuated vaccine immunization has resulted in impressive success in the redn. and control of infectious disease outbreaks. However, many pathogens remain less amenable to deal with the traditional vaccine strategies, and more appropriate vaccine strategy is in need. Recent discoveries that led to increased understanding of viral mol. biol. and genetics has rendered the used of viruses as vaccine platforms and as potential anti-cancer agents. Due to their ability to effectively induce both humoral and cell-mediated immune responses, viral vectors are deemed as an attractive alternative to the traditional platforms to deliver vaccine antigens as well as to specifically target and kill tumor cells. With potential targets ranging from cancers to a vast no. of infectious diseases, the benefits resulting from successful application of viral vectors to prevent and treat human diseases can be immense.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhtlWksLrI&md5=b4881747ccbd81ec3110f948216d660b
  69. 69
    Draper, S. J.; Heeney, J. L. Viruses as Vaccine Vectors for Infectious Diseases and Cancer. Nat. Rev. Microbiol. 2010, 8, 62– 73,  DOI: 10.1038/nrmicro2240
    Google Scholar
    69
    Viruses as vaccine vectors for infectious diseases and cancer
    Draper, Simon J.; Heeney, Jonathan L.
    Nature Reviews Microbiology (2010), 8 (1), 62-73CODEN: NRMACK; ISSN:1740-1526. (Nature Publishing Group)
    A review. Recent developments in the use of viruses as vaccine vectors have been facilitated by a better understanding of viral biol. Advances occur as we gain greater insight into the interrelationship of viruses and the immune system. Viral-vector vaccines remain the best means to induce cellular immunity and are now showing promise for the induction of strong humoral responses. The potential benefits for global health that are offered by this field reflect the scope and utility of viruses as vaccine vectors for human and veterinary applications, with targets ranging from certain types of cancer to a vast array of infectious diseases.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXhsFWksb%252FO&md5=d7d240377ee6d8ca8930b56c292f6aba
  70. 70
    Ura, T.; Okuda, K.; Shimada, M. Developments in Viral Vector-Based Vaccines. Vaccines (Basel, Switz.) 2014, 2, 624– 641,  DOI: 10.3390/vaccines2030624
    Google Scholar
    70
    Developments in viral vector-based vaccines
    Ura, Takehiro; Okuda, Kenji; Shimada, Masaru
    Vaccines (Basel, Switzerland) (2014), 2 (3), 624-641, 18 pp.CODEN: VBSABP; ISSN:2076-393X. (MDPI AG)
    A review. Viral vectors are promising tools for gene therapy and vaccines. Viral vector-based vaccines can enhance immunogenicity without an adjuvant and induce a robust cytotoxic T lymphocyte (CTL) response to eliminate virus-infected cells. During the last several decades, many types of viruses have been developed as vaccine vectors. Each has unique features and parental virus-related risks. In addn., genetically altered vectors have been developed to improve efficacy and safety, reduce administration dose, and enable large-scale manufg. To date, both successful and unsuccessful results have been reported in clin. trials. These trials provide important information on factors such as toxicity, administration dose tolerated, and optimized vaccination strategy. This review highlights major viral vectors that are the best candidates for clin. use.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhvFagsr%252FI&md5=2e7a465adbf48ad48378fad19af03842
  71. 71
    Pardi, N.; Tuyishime, S.; Muramatsu, H.; Kariko, K.; Mui, B. L.; Tam, Y. K.; Madden, T. D.; Hope, M. J.; Weissman, D. Expression Kinetics of Nucleoside-Modified MRNA Delivered in Lipid Nanoparticles to Mice by Various Routes. J. Controlled Release 2015, 217, 345– 351,  DOI: 10.1016/j.jconrel.2015.08.007
    Google Scholar
    71
    Expression kinetics of nucleoside-modified mRNA delivered in lipid nanoparticles to mice by various routes
    Pardi, Norbert; Tuyishime, Steven; Muramatsu, Hiromi; Kariko, Katalin; Mui, Barbara L.; Tam, Ying K.; Madden, Thomas D.; Hope, Michael J.; Weissman, Drew
    Journal of Controlled Release (2015), 217 (), 345-351CODEN: JCREEC; ISSN:0168-3659. (Elsevier B.V.)
    In recent years, in vitro transcribed mRNA (mRNA) has emerged as a potential therapeutic platform. To fulfill its promise, effective delivery of mRNA to specific cell types and tissues needs to be achieved. Lipid nanoparticles (LNPs) are efficient carriers for short-interfering RNAs and have entered clin. trials. However, little is known about the potential of LNPs to deliver mRNA. Here, we generated mRNA-LNPs by incorporating HPLC purified, 1-methylpseudouridine-contg. mRNA comprising codon-optimized firefly luciferase into stable LNPs. Mice were injected with 0.005-0.250 mg/kg doses of mRNA-LNPs by 6 different routes and high levels of protein translation could be measured using in vivo imaging. S.c., i.m. and intradermal injection of the LNP-encapsulated mRNA translated locally at the site of injection for up to 10 days. For several days, high levels of protein prodn. could be achieved in the lung from the intratracheal administration of mRNA. I.v. and i.p. and to a lesser extent i.m. and intratracheal deliveries led to trafficking of mRNA-LNPs systemically resulting in active translation of the mRNA in the liver for 1-4 days. Our results demonstrate that LNPs are appropriate carriers for mRNA in vivo and have the potential to become valuable tools for delivering mRNA encoding therapeutic proteins.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhsV2msr%252FE&md5=35c5150ee9a95ee66bf13786d14b3469
  72. 72
    Dalpke, A. H.; Helm, M. RNA Mediated Toll-Like Receptor Stimulation in Health and Disease. RNA Biol. 2012, 9, 828– 842,  DOI: 10.4161/rna.20206
    Google Scholar
    72
    RNA mediated toll-like receptor stimulation in health and disease
    Dalpke, Alexander H.; Helm, Mark
    RNA Biology (2012), 9 (6), 828-842CODEN: RBNIBE; ISSN:1547-6286. (Landes Bioscience)
    A review. Besides their well-known functions in storage and translation of information, nucleic acids have emerged as a target of pattern recognition receptors that drive activation of innate immunity. Due to the paucity of building block monomers used in nucleic acids, discrimination of host and microbial nucleic acids as a means of self/foreign discrimination is a complicated task. Pattern recognition receptors rely on discrimination by sequence, structural features and spatial compartmentalization to differentiate microbial derived nucleic acids from host ones. Microbial nucleic acid detection is important for the sensing of infectious danger and initiating an immune response to microbial attack. Failures in the underlying recognitions systems can have severe consequences. Thus, inefficient recognition of microbial nucleic acids may increase susceptibility to infectious diseases. On the other hand, excessive immune responses as a result of failed self/foreign discrimination are assocd. with autoimmune diseases. This review gives a general overview over the underlying concepts of nucleic acid sensing by Toll-like receptors. Within this general framework, we focus on bacterial RNA and synthetic RNA oligomers.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXpsVOhsA%253D%253D&md5=7fb843ce076ecf749cc525cdb6704512
  73. 73
    Heil, F.; Hemmi, H.; Hochrein, H.; Ampenberger, F.; Kirschning, C.; Akira, S.; Lipford, G.; Wagner, H.; Bauer, S. Species-Specific Recognition of Single-Stranded RNA via Toll-Like Receptor 7 and 8. Science 2004, 303, 1526– 1529,  DOI: 10.1126/science.1093620
    Google Scholar
    73
    Species-Specific Recognition of Single-Stranded RNA via Toll-like Receptor 7 and 8
    Heil, Florian; Hemmi, Hiroaki; Hochrein, Hubertus; Ampenberger, Franziska; Kirschning, Carsten; Akira, Shizuo; Lipford, Grayson; Wagner, Hermann; Bauer, Stefan
    Science (Washington, DC, United States) (2004), 303 (5663), 1526-1529CODEN: SCIEAS; ISSN:0036-8075. (American Association for the Advancement of Science)
    Double-stranded RNA (dsRNA) serves as a danger signal assocd. with viral infection and leads to stimulation of innate immune cells. In contrast, the immunostimulatory potential of single-stranded RNA (ssRNA) is poorly understood and innate immune receptors for ssRNA are unknown. The authors report that guanosine (G)- and uridine (U)-rich ssRNA oligonucleotides derived from human immunodeficiency virus-1 (HIV-1) stimulate dendritic cells (DC) and macrophages to secrete interferon-α and proinflammatory, as well as regulatory, cytokines. By using Toll-like receptor (TLR)-deficient mice and genetic complementation, the authors show that murine TLR7 and human TLR8 mediate species-specific recognition of GU-rich ssRNA. These data suggest that ssRNA represents a physiol. ligand for TLR7 and TLR8.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2cXhslCgsLc%253D&md5=33596446b6a66f5d3f9137eb83aaa242
  74. 74
    Zhang, C.; Maruggi, G.; Shan, H.; Li, J. Advances in MRNA Vaccines for Infectious Diseases. Front. Immunol. 2019, 10, 594,  DOI: 10.3389/fimmu.2019.00594
    Google Scholar
    74
    Advances in mRNA vaccines for infectious diseases
    Zhang, Cuiling; Maruggi, Giulietta; Shan, Hu; Li, Junwei
    Frontiers in Immunology (2019), 10 (), 594CODEN: FIRMCW; ISSN:1664-3224. (Frontiers Media S.A.)
    A review. During the last two decades, there has been broad interest in RNA-based technologies for the development of prophylactic and therapeutic vaccines. Preclin. and clin. trials have shown that mRNA vaccines provide a safe and long-lasting immune response in animal models and humans. In this , we summarize current research progress on mRNA vaccines, which have the potential to be quick-manufd. and to become powerful tools against infectious disease and we highlight the bright future of their design and applications.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXhtlKhtbjK&md5=687f022a6bad0206ed845775c61f0e39
  75. 75
    Safety and Immunogenicity Study of 2019-nCoV Vaccine (mRNA-1273) for Prophylaxis SARS CoV-2 Infection - Full Text View. ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT04283461 (accessed 2020-04-03).
    Google Scholar
    There is no corresponding record for this reference.
  76. 76
    Study to Describe the Safety, Tolerability, Immunogenicity, and Potential Efficacy of RNA Vaccine Candidates against COVID-19 in Healthy Adults - Full Text View. ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT04368728 (accessed 2020-05-21).
    Google Scholar
    There is no corresponding record for this reference.
  77. 77
    A Multi-Site, Phase I/II, 2-Part, Dose-Escalation Trial Investigating the Safety and Immunogenicity of Four Prophylactic SARS-CoV-2 RNA Vaccines against COVID-2019 Using Different Dosing Regimens in Healthy Adults - Full Text View. ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT04380701 (accessed 2020-05-21).
    Google Scholar
    There is no corresponding record for this reference.
  78. 78
    A Phase I/II Study to Determine Efficacy, Safety and Immunogenicity of the Candidate Coronavirus Disease (COVID-19) Vaccine ChAdOx1 NCoV-19 in UK Healthy Adult Volunteers - Full Text View. ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT04324606 (accessed 2020-05-21).
    Google Scholar
    There is no corresponding record for this reference.
  79. 79
    Phase I Clinical Trial of a COVID-19 Vaccine in 18–60 Healthy Adults - Full Text View. ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT04313127 (accessed 2020-05-27).
    Google Scholar
    There is no corresponding record for this reference.
  80. 80
    A Phase II Clinical Trial to Evaluate the Recombinant Vaccine for COVID-19 (Adenovirus Vector) - Full Text View. ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT04341389 (accessed 2020-05-27).
    Google Scholar
    There is no corresponding record for this reference.
  81. 81
    Safety, Tolerability and Immunogenicity of INO-4800 for COVID-19 in Healthy Volunteers - Full Text View. ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT04336410 (accessed 2020-04-10).
    Google Scholar
    There is no corresponding record for this reference.
  82. 82
    INOVIO Announces Positive Interim Phase 1 Data For INO-4800 Vaccine for COVID-19. http://ir.inovio.com/news-releases/news-releases-details/2020/INOVIO-Announces-Positive-Interim-Phase-1-Data-For-INO-4800-Vaccine-for-COVID-19/default.aspx (accessed 2020-07-21).
    Google Scholar
    There is no corresponding record for this reference.
  83. 83
    A Randomized, Double-Blinded, Placebo-Controlled, Phase I/II Clinical Trial, to Evaluate the Safety and Immunogenicity of the SARS-CoV-2 Inactivated Vaccine (Vero Cell) in Healthy Population Aged ≥ 60 Years - Full Text View. ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT04383574 (accessed 2020-05-21).
    Google Scholar
    There is no corresponding record for this reference.
  84. 84
    Sinovac Reports Positive Data from Phase I/II trials of CoronaVac https://www.clinicaltrialsarena.com/news/sinovac-coronavac-data/ (accessed 2020-08-14).
    Google Scholar
    There is no corresponding record for this reference.
  85. 85
    China Sinopharm’s Potential COVID-19 Vaccine Triggers Antibodies in Clinical Trials: Journal. Reuters. 2020-08-14.
    Google Scholar
    There is no corresponding record for this reference.
  86. 86
    Novel Coronavirus (2019-CoV) Inactivated Vaccine (Vero Cell) Phase I/II Clinical Trial. http://www.chictr.org.cn/showproj.aspx?proj=53003 (accessed 2020-08-14).
    Google Scholar
    There is no corresponding record for this reference.
  87. 87
    http://www.chictr.org.cn/showproj.aspx?proj=53003 (accessed 2020-08-14).
    Google Scholar
    There is no corresponding record for this reference.
  88. 88
    First COVID-19 Inactivated Vaccine Performs Well in Clinical Trials. http://en.sasac.gov.cn/2020/07/02/c_5178.htm (accessed 2020-08-14).
    Google Scholar
    There is no corresponding record for this reference.
  89. 89
    An Open Study of the Safety, Tolerability and Immunogenicity of the Drug “Gam-COVID-Vac” Vaccine against COVID-19 - Full Text View. ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT04436471 (accessed 2020-08-03).
    Google Scholar
    There is no corresponding record for this reference.
  90. 90
    An Open Study of the Safety, Tolerability and Immunogenicity of “Gam-COVID-Vac Lyo” Vaccine against COVID-19 - Full Text View. ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT04437875 (accessed 2020-08-03).
    Google Scholar
    There is no corresponding record for this reference.
  91. 91
    China’s Zhifei Starts Phase II Trial of COVID-19 Vaccine. Reuters . July 10, 2020. 7 10 DOI: 10.1089/clinomi.07.04.17
    Google Scholar
    There is no corresponding record for this reference.
  92. 92
    Phase I Clinical Study of Recombinant Novel Coronavirus Vaccine - Full Text View. ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT04445194 (accessed 2020-08-14).
    Google Scholar
    There is no corresponding record for this reference.
  93. 93
    A 2-Part, Phase 1/2, Randomized, Observer-Blinded Study to Evaluate the Safety and Immunogenicity of a SARS-CoV-2 Recombinant Spike Protein Nanoparticle Vaccine (SARS-CoV-2 RS) with or without MATRIX-MTM Adjuvant in Healthy Subjects - Full Text View. ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT04368988 (accessed 2020-08-14).
    Google Scholar
    There is no corresponding record for this reference.
  94. 94
    Chowdhury, D. Vaxine Expects to Start Phase II Trials for Potential COVID-19 Vaccine in Weeks. Reuters . July 29, 2020.
    Google Scholar
    There is no corresponding record for this reference.
  95. 95
    Monovalent Recombinant COVID19 Vaccine - Full Text View. ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT04453852 (accessed 2020-08-14).
    Google Scholar
    There is no corresponding record for this reference.
  96. 96
    Zydus Cadila’s COVID-19 Vaccine Passes Phase I Safety Trials; Phase II to Test Efficiency Begins 6 August - Health News, Firstpost. https://www.firstpost.com/health/zydus-cadilas-covid-19-vaccine-passes-phase-i-safety-trials-phase-ii-to-test-efficiency-begins-6-august-8674891.html (accessed 2020-08-14).
    Google Scholar
    There is no corresponding record for this reference.
  97. 97
    Kaur, S. P.; Gupta, V. COVID-19 Vaccine: A Comprehensive Status Report. Virus Res. 2020, 288, 198114,  DOI: 10.1016/j.virusres.2020.198114
    Google Scholar
    97
    COVID-19 Vaccine: A comprehensive status report
    Kaur, Simran Preet; Gupta, Vandana
    Virus Research (2020), 288 (), 198114CODEN: VIREDF; ISSN:0168-1702. (Elsevier B.V.)
    A review. The current COVID-19 pandemic has urged the scientific community internationally to find answers in terms of therapeutics and vaccines to control SARS-CoV-2. Published investigations mostly on SARS-CoV and to some extent on MERS has taught lessons on vaccination strategies to this novel coronavirus. This is attributed to the fact that SARS-CoV-2 uses the same receptor as SARS-CoV on the host cell i.e. human Angiotensin Converting Enzyme 2 (hACE2) and is approx. 79% similar genetically to SARS-CoV. Though the efforts on COVID-19 vaccines started very early, initially in China, as soon as the outbreak of novel coronavirus erupted and then world-over as the disease was declared a pandemic by WHO. But we will not be having an effective COVID-19 vaccine before Sept., 2020 as per very optimistic ests. This is because a successful COVID-19 vaccine will require a cautious validation of efficacy and adverse reactivity as the target vaccinee population include high-risk individuals over the age of 60, particularly those with chronic co-morbid conditions, frontline healthcare workers and those involved in essentials industries. Various platforms for vaccine development are available namely: virus vectored vaccines, protein subunit vaccines, genetic vaccines, and monoclonal antibodies for passive immunization which are under evaluations for SARS-CoV-2, with each having discrete benefits and hindrances. The COVID-19 pandemic which probably is the most devastating one in the last 100 years after Spanish flu mandates the speedy evaluation of the multiple approaches for competence to elicit protective immunity and safety to curtail unwanted immune-potentiation which plays an important role in the pathogenesis of this virus. This review is aimed at providing an overview of the efforts dedicated to an effective vaccine for this novel coronavirus which has crippled the world in terms of economy, human health and life.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhslejtbfJ&md5=f8319a3df3554fe84038210738752ccf
  98. 98
    COVID-19 Vaccine Reaches Phase-2 Trials in China. http://english.nmpa.gov.cn/2020-06/22/c_502093.htm (accessed 2020-08-14).
    Google Scholar
    There is no corresponding record for this reference.
  99. 99
    Safety and Immunogenicity Study of an Inactivated SARS-CoV-2 Vaccine for Preventing against COVID-19 in People Aged ⩾60 Years - Full Text View. ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT04470609 (accessed 2020-08-14).
    Google Scholar
    There is no corresponding record for this reference.
  100. 100
    Richner, J. M.; Himansu, S.; Dowd, K. A.; Butler, S. L.; Salazar, V.; Fox, J. M.; Julander, J. G.; Tang, W. W.; Shresta, S.; Pierson, T. C.; Ciaramella, G.; Diamond, M. S. Modified MRNA Vaccines Protect against Zika Virus Infection. Cell 2017, 168, 1114– 1125,  DOI: 10.1016/j.cell.2017.02.017
    Google Scholar
    100
    Modified mRNA vaccines protect against Zika virus infection
    Richner, Justin M.; Himansu, Sunny; Dowd, Kimberly A.; Butler, Scott L.; Salazar, Vanessa; Fox, Julie M.; Julander, Justin G.; Tang, William W.; Shresta, Sujan; Pierson, Theodore C.; Ciaramella, Giuseppe; Diamond, Michael S.
    Cell (Cambridge, MA, United States) (2017), 168 (6), 1114-1125.e10CODEN: CELLB5; ISSN:0092-8674. (Cell Press)
    The emergence of ZIKV infection has prompted a global effort to develop safe and effective vaccines. We engineered a lipid nanoparticle (LNP) encapsulated modified mRNA vaccine encoding wild-type or variant ZIKV structural genes and tested immunogenicity and protection in mice. Two doses of modified mRNA LNPs encoding prM-E genes that produced virus-like particles resulted in high neutralizing antibody titers (∼1/100,000) that protected against ZIKV infection and conferred sterilizing immunity. To offset a theor. concern of ZIKV vaccines inducing antibodies that cross-react with the related dengue virus (DENV), we designed modified prM-E RNA encoding mutations destroying the conserved fusion-loop epitope in the E protein. This variant protected against ZIKV and diminished prodn. of antibodies enhancing DENV infection in cells or mice. A modified mRNA vaccine can prevent ZIKV disease and be adapted to reduce the risk of sensitizing individuals to subsequent exposure to DENV, should this become a clin. relevant concern.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXivFensL8%253D&md5=2073ac40e1d084844ae808586333cb29
  101. 101
    Perrie, Y.; Crofts, F.; Devitt, A.; Griffiths, H. R.; Kastner, E.; Nadella, V. Designing Liposomal Adjuvants for the Next Generation of Vaccines. Adv. Drug Delivery Rev. 2016, 99 (Pt A), 85– 96,  DOI: 10.1016/j.addr.2015.11.005
    Google Scholar
    101
    Designing liposomal adjuvants for the next generation of vaccines
    Perrie, Yvonne; Crofts, Fraser; Devitt, Andrew; Griffiths, Helen R.; Kastner, Elisabeth; Nadella, Vinod
    Advanced Drug Delivery Reviews (2016), 99 (Part_A), 85-96CODEN: ADDREP; ISSN:0169-409X. (Elsevier B.V.)
    Liposomes not only offer the ability to enhance drug delivery, but can effectively act as vaccine delivery systems and adjuvants. Their flexibility in size, charge, bilayer rigidity and compn. allow for targeted antigen delivery via a range of administration routes. In the development of liposomal adjuvants, the type of immune response promoted has been linked to their physico-chem. characteristics, with the size and charge of the liposomal particles impacting on liposome biodistribution, exposure in the lymph nodes and recruitment of the innate immune system. The addn. of immunostimulatory agents can further potentiate their immunogenic properties. Here, we outline the attributes that should be considered in the design and manuf. of liposomal adjuvants for the delivery of sub-unit and nucleic acid based vaccines.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhvVChs7vL&md5=0a957b1de59d473966e0722a1d381203
  102. 102
    Karikó, K.; Muramatsu, H.; Welsh, F. A.; Ludwig, J.; Kato, H.; Akira, S.; Weissman, D. Incorporation of Pseudouridine into MRNA Yields Superior Nonimmunogenic Vector with Increased Translational Capacity and Biological Stability. Mol. Ther. 2008, 16, 1833– 1840,  DOI: 10.1038/mt.2008.200
    Google Scholar
    102
    Incorporation of pseudouridine into mRNA yields superior nonimmunogenic vector with increased translational capacity and biological stability
    Kariko, Katalin; Muramatsu, Hiromi; Welsh, Frank A.; Ludwig, Janos; Kato, Hiroki; Akira, Shizuo; Weissman, Drew
    Molecular Therapy (2008), 16 (11), 1833-1840CODEN: MTOHCK; ISSN:1525-0016. (Nature Publishing Group)
    In vitro-transcribed mRNAs encoding physiol. important proteins have considerable potential for therapeutic applications. However, in its present form, mRNA is unfeasible for clin. use because of its labile and immunogenic nature. Here, we investigated whether incorporation of naturally modified nucleotides into transcripts would confer enhanced biol. properties to mRNA. We found that mRNAs contg. pseudouridines have a higher translational capacity than unmodified mRNAs when tested in mammalian cells and lysates or administered i.v. into mice at 0.015-0.15 mg/kg doses. The delivered mRNA and the encoded protein could be detected in the spleen at 1, 4, and 24 h after the injection, where both products were at significantly higher levels when pseudouridine-contg. mRNA was administered. Even at higher doses, only the unmodified mRNA was immunogenic, inducing high serum levels of interferon-α (IFN-α). These findings indicate that nucleoside modification is an effective approach to enhance stability and translational capacity of mRNA while diminishing its immunogenicity in vivo. Improved properties conferred by pseudouridine make such mRNA a promising tool for both gene replacement and vaccination.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1cXht12ls7vK&md5=3e575d74308b37b8598a633cd82f3873
  103. 103
    Naylor, R.; Ho, N. W.; Gilham, P. T. Selective Chemical Modifications of Uridine and Pseudouridine in Polynucleotides and Their Effect on the Specificities of Ribonuclease and Phosphodiesterases. J. Am. Chem. Soc. 1965, 87, 4209– 4210,  DOI: 10.1021/ja01096a050
    Google Scholar
    103
    Selective chemical modifications of uridine and pseudouridine in polynucleotides and their effect on the specificities of ribonuclease and phosphodiesterases
    Naylor, R.; Ho, Nancy W. Y.; Gilham, P. T.
    Journal of the American Chemical Society (1965), 87 (18), 4209-10CODEN: JACSAT; ISSN:0002-7863.
    1-Cyclohexyl-3-(2-morpholinoethyl)carbodiimide metho-p-toluenesulfonate (CMC) added specifically to uridine and guanosine components of RNA such that the modified uridine bases become resistant to the action of pancreatic RNase ( CA 57, 2587d). As a result, digestion of the modified RNA with this enzyme produces oligonucleotides which terminate with cytidine only (CA 63, 833g). When amino acid acceptor RNA from yeast was treated with CMC and hydrolyzed with RNase, no pseudouridine phosphate, uridine phosphate, or corresponding cyclic phosphates were produced. Thus, it appears that pseudouridine is also blocked under the conditions necessary for the blocking of uridine and guanosine. Furthermore, if the modified RNA was treated with dil. NH4OH to remove the blocking groups and then hydrolyzed with RNase, the products obtained were similar to those obtained by the enzymic digestion of untreated RNA except that, in the former case, no pseudouridine phosphate or cyclic phosphate was formed. These results indicate that the pseudouridine bases in RNA form stable adducts with CMC and that the resistance of these adducts to RNase hydrolysis results in the pseudouridine components being left in internal positions of the oligonucleotides that remain after the enzymic digestion. These conclusions were confirmed by a study of the chem. blocking of pseudouridine itself. The rates of hydrolysis of various synthetic dinucleoside phosphates with snake venom and spleen diesterases were tabulated and discussed.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaF2MXkvFSmtLo%253D&md5=379a8ebc183d3b7c20889d37f93dbbab
  104. 104
    Davis, D. R. Stabilization of RNA Stacking by Pseudouridine. Nucleic Acids Res. 1995, 23, 5020– 5026,  DOI: 10.1093/nar/23.24.5020
    Google Scholar
    104
    Stabilization of RNA stacking by pseudouridine
    Davis, Darrell R.
    Nucleic Acids Research (1995), 23 (24), 5020-6CODEN: NARHAD; ISSN:0305-1048. (Oxford University Press)
    The effect of the modified nucleoside pseudouridine (Ψ) on RNA structure was compared with uridine. The extent of base stacking in model RNA oligonucleotides was measured by 1H NMR, UV, and CD spectroscopy. The UV and CD results indicate that the model single-stranded oligoribonucleotides AAUA and AAΨA from stacked structures in soln. and the CD results for AAΨA are consistent with a general A-form helical conformation. The AAΨA oligomer exhibits a greater degree of UV hypochromicity over the temp. range 5-55°, consistent with a better stacked, more A-form structure compared with AAUA. The extent of stacking for each nucleotide residue was inferred from the percent 3'-endo sugar conformation as indicated by the H1'-H2' NMR scalar coupling. This indirect indication of stacking was confirmed by sequential NOE connectivity patterns obtained from 2D ROESY NMR expts. NMR measurements as a function of temp. indicate that pseudouridine forms a more stable base stacking arrangement than uridine, an effect that is propagated throughout the helix to stabilize stacking of neighboring purine nucleosides. The N1-H imino proton in AAΨA exchanges slowly with solvent, suggesting a role for the extra imino proton in stabilizing the conformation of pseudouridine. These results show that the conformational stabilization is an intrinsic property of pseudouridine occurring at the nucleotide level. The characteristics of pseudouridine in these models are consistent with earlier studies on intact tRNA, indicating that pseudouridine probably performs the same stabilizing function in most structural contexts.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK28XlsVCktg%253D%253D&md5=b1284db31e2266ee1593e3b377ec79a5
  105. 105
    Tai, W.; Zhao, G.; Sun, S.; Guo, Y.; Wang, Y.; Tao, X.; Tseng, C.-T. K.; Li, F.; Jiang, S.; Du, L.; Zhou, Y. A Recombinant Receptor-Binding Domain of MERS-CoV in Trimeric Form Protects Human Dipeptidyl Peptidase 4 (HDPP4) Transgenic Mice from MERS-CoV Infection. Virology 2016, 499, 375– 382,  DOI: 10.1016/j.virol.2016.10.005
    Google Scholar
    105
    A recombinant receptor-binding domain of MERS-CoV in trimeric form protects human dipeptidyl peptidase 4 (hDPP4) transgenic mice from MERS-CoV infection
    Tai, Wanbo; Zhao, Guangyu; Sun, Shihun; Guo, Yan; Wang, Yufei; Tao, Xinrong; Tseng, Chien-Te K.; Li, Fang; Jiang, Shibo; Du, Lanying; Zhou, Yusen
    Virology (2016), 499 (), 375-382CODEN: VIRLAX; ISSN:0042-6822. (Elsevier B.V.)
    Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV) was first identified in 2012, and it continues to threaten human health worldwide. No MERS vaccines are licensed for human use, reinforcing the urgency to develop safe and efficacious vaccines to prevent MERS. MERS-CoV spike protein forms a trimer, and its receptor-binding domain (RBD) serves as a vaccine target. Nevertheless, the protective efficacy of RBD in its native trimeric form has never been evaluated. In this study, a trimeric protein, RBD-Fd, was generated by fusing RBD with foldon trimerization motif. It bound strongly to the receptor of MERS-CoV, dipeptidyl peptidase 4 (DPP4), and elicited robust RBD-specific neutralizing antibodies in mice, maintaining long-term neutralizing activity against MERS-CoV infection. RBD-Fd potently protected hDPP4 transgenic mice from lethal MERS-CoV challenge. These results suggest that MERS-CoV RBD in its trimeric form maintains native conformation and induces protective neutralizing antibodies, making it a candidate for further therapeutic development.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28Xhs1yqsbzM&md5=c372450b91d5d39330143c81166f764e
  106. 106
    A Study to Evaluate Efficacy, Safety, and Immunogenicity of mRNA-1273 Vaccine in Adults Aged 18 Years and Older to Prevent COVID-19 - Full Text View. ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT04470427 (accessed 2020-08-10).
    Google Scholar
    There is no corresponding record for this reference.
  107. 107
    Study to Describe the Safety, Tolerability, Immunogenicity, and Efficacy of RNA Vaccine Candidates against COVID-19 in Healthy Adults - Full Text View. ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT04368728 (accessed 2020-08-03).
    Google Scholar
    There is no corresponding record for this reference.
  108. 108
    INO-4800 DNA Coronavirus Vaccine https://www.precisionvaccinations.com/vaccines/ino-4800-dna-coronavirus-vaccine (accessed 2020-08-14).
    Google Scholar
    There is no corresponding record for this reference.
  109. 109
    Cohen, J. with Record-Setting Speed, Vaccinemakers Take Their First Shots at the New Coronavirus. https://www.sciencemag.org/news/2020/03/record-setting-speed-vaccine-makers-take-their-first-shots-new-coronavirus (accessed 2020-08-14).
    Google Scholar
    There is no corresponding record for this reference.
  110. 110
    Lowe, D. The Russian Vaccine. https://blogs.sciencemag.org/pipeline/archives/2020/08/11/the-russian-vaccine (accessed 2020-08-14).
    Google Scholar
    There is no corresponding record for this reference.
  111. 111
    Skepticism Greets Putin’s Announcement Of Russian Coronavirus Vaccine. https://www.npr.org/sections/coronavirus-live-updates/2020/08/11/901270401/skepticism-greets-putins-announcement-of-russian-coronavirus-vaccine (accessed 2020-08-14).
    Google Scholar
    There is no corresponding record for this reference.
  112. 112
    Closing in on a COVID-19 Vaccine. https://www.eurekalert.org/pub_releases/2020-04/fu-cio040220.php (accessed 2020-04-19).
    Google Scholar
    There is no corresponding record for this reference.
  113. 113
    Dicks, M. D. J.; Spencer, A. J.; Edwards, N. J.; Wadell, G.; Bojang, K.; Gilbert, S. C.; Hill, A. V. S.; Cottingham, M. G. A Novel Chimpanzee Adenovirus Vector with Low Human Seroprevalence: Improved Systems for Vector Derivation and Comparative Immunogenicity. PLoS One 2012, 7, e40385  DOI: 10.1371/journal.pone.0040385
    Google Scholar
    113
    A novel chimpanzee adenovirus vector with low human seroprevalence: improved systems for vector derivation and comparative immunogenicity
    Dicks, Matthew D. J.; Spencer, Alexandra J.; Edwards, Nick J.; Wadell, Goeran; Bojang, Kalifa; Gilbert, Sarah C.; Hill, Adrian V. S.; Cottingham, Matthew G.
    PLoS One (2012), 7 (7), e40385CODEN: POLNCL; ISSN:1932-6203. (Public Library of Science)
    Recombinant adenoviruses are among the most promising tools for vaccine antigen delivery. Recently, the development of new vectors has focused on serotypes to which the human population is less exposed in order to circumvent pre-existing anti vector immunity. This study describes the derivation of a new vaccine vector based on a chimpanzee adenovirus, Y25, together with a comparative assessment of its potential to elicit transgene product specific immune responses in mice. The vector was constructed in a bacterial artificial chromosome to facilitate genetic manipulation of genomic clones. In order to conduct a fair head-to-head immunol. comparison of multiple adenoviral vectors, we optimized a method for accurate detn. of infectious titer, since this parameter exhibits profound natural variability and can confound immunogenicity studies when doses are based on viral particle estn. Cellular immunogenicity of recombinant E1 E3-deleted vector ChAdY25 was comparable to that of other species E derived chimpanzee adenovirus vectors including ChAd63, the first simian adenovirus vector to enter clin. trials in humans. Furthermore, the prevalence of virus neutralizing antibodies (titer >1:200) against ChAdY25 in serum samples collected from two human populations in the UK and Gambia was particularly low compared to published data for other chimpanzee adenoviruses. These findings support the continued development of new chimpanzee adenovirus vectors, including ChAdY25, for clin. use.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhtVyisrvN&md5=dc7f267cde7ad2f6916097d25923a9fc
  114. 114
    Li, L.; Petrovsky, N. Molecular Mechanisms for Enhanced DNA Vaccine Immunogenicity. Expert Rev. Vaccines 2016, 15, 313– 329,  DOI: 10.1586/14760584.2016.1124762
    Google Scholar
    114
    Molecular mechanisms for enhanced DNA vaccine immunogenicity
    Li, Lei; Petrovsky, Nikolai
    Expert Review of Vaccines (2016), 15 (3), 313-329CODEN: ERVXAX; ISSN:1476-0584. (Taylor & Francis Ltd.)
    In the two decades since their initial discovery, DNA vaccines technologies have come a long way. Unfortunately, when applied to human subjects inadequate immunogenicity is still the biggest challenge for practical DNA vaccine use. Many different strategies have been tested in preclin. models to address this problem, including novel plasmid vectors and codon optimization to enhance antigen expression, new gene transfection systems or electroporation to increase delivery efficiency, protein or live virus vector boosting regimens to maximise immune stimulation, and formulation of DNA vaccines with traditional or mol. adjuvants. Better understanding of the mechanisms of action of DNA vaccines has also enabled better use of the intrinsic host response to DNA to improve vaccine immunogenicity. This review summarizes recent advances in DNA vaccine technologies and related intracellular events and how these might impact on future directions of DNA vaccine development.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXitV2msbnJ&md5=fabe70b4f42c741d0fc1086b6e6abc84
  115. 115
    Coughlan, L. Factors Which Contribute to the Immunogenicity of Non-Replicating Adenoviral Vectored Vaccines. Front. Immunol. 2020, 11. DOI: 10.3389/fimmu.2020.00909
    Google Scholar
    There is no corresponding record for this reference.
  116. 116
    CanSino to Conduct Phase III Covid-19 Vaccine Trial in Saudi Arabia. https://www.clinicaltrialsarena.com/news/cansino-vaccine-saudi-trial/ (accessed 2020-08-10).
    Google Scholar
    There is no corresponding record for this reference.
  117. 117
    A Phase III Study to Investigate a Vaccine against COVID-19. http://www.isrctn.com/ISRCTN89951424 (accessed 2020-08-10).
    Google Scholar
    There is no corresponding record for this reference.
  118. 118
    Ella, K. M.; Mohan, V. K. Coronavirus Vaccine: Light at the End of the Tunnel. Indian Pediatr. 2020, 57, 407– 410,  DOI: 10.1007/s13312-020-1812-z
    Google Scholar
    118
    Coronavirus Vaccine: Light at the End of the Tunnel
    Ella Krishna M; Mohan V Krishna
    Indian pediatrics (2020), 57 (5), 407-410 ISSN:.
    The world is currently facing an unprecedented global pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Predicting the next source of the pandemic can be very challenging. As vaccination is the best way to prevent an infectious disease, the development of an effective vaccine against SARS-CoV-2 can not only reduce the morbidity and mortality associated with it, but can also lessen the economic impact. As the traditional method of vaccine development takes many years for a vaccine to be available to the society, the vaccine development for SARS-CoV-2 should be speeded up using a pandemic approach with fast-track approvals from the regulatory authorities. Various challenges associated with developing a vaccine during the pandemic such as technological hurdles, clinical development pathways, regulatory issues, and support from global funding agencies are expressed here.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB38zltlaqtQ%253D%253D&md5=a267cd0fd76ae1849d65f711902e2210
  119. 119
    Genexine, Y Biologics to Co-Develop Covid-19 Treatment - Korea Biomedical Review. http://www.koreabiomed.com/news/articleView.html?idxno=8800 (accessed 2020-08-03).
    Google Scholar
    There is no corresponding record for this reference.
  120. 120
    Japan’s AnGes Speeds Toward 2021 Rollout in Coronavirus “Vaccine War. https://www.japantimes.co.jp/news/2020/06/11/national/science-health/anges-coronavirus-vaccine-war/ (accessed 2020-08-03).
    Google Scholar
    There is no corresponding record for this reference.
  121. 121
    Weiner, D. B. RNA-Based Vaccination: Sending a Strong Message. Mol. Ther. 2013, 21, 506– 508,  DOI: 10.1038/mt.2013.26
    Google Scholar
    121
    RNA-Based Vaccination: Sending a Strong Message
    Weiner, David B.
    Molecular Therapy (2013), 21 (3), 506-508CODEN: MTOHCK; ISSN:1525-0016. (Nature Publishing Group)
    A review. This commentary reports on nucleic acid-based vaccines (NAVs) for induction of antigen-specific immunity and their emergence as important tools in our vaccine/immune therapeutic arsenal.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXjtlaksb0%253D&md5=e335f7c4d635d8f7952945de9b88cff2
  122. 122
    Watanabe, Y.; Allen, J. D.; Wrapp, D.; McLellan, J. S.; Crispin, M. Site-Specific Glycan Analysis of the SARS-CoV-2 Spike. Science 2020, 369, 330– 333,  DOI: 10.1126/science.abb9983
    Google Scholar
    122
    Site-specific glycan analysis of the SARS-CoV-2 spike
    Watanabe, Yasunori; Allen, Joel D.; Wrapp, Daniel; McLellan, Jason S.; Crispin, Max
    Science (Washington, DC, United States) (2020), 369 (6501), 330-333CODEN: SCIEAS; ISSN:1095-9203. (American Association for the Advancement of Science)
    The emergence of the betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), represents a considerable threat to global human health. Vaccine development is focused on the principal target of the humoral immune response, the spike (S) glycoprotein, which mediates cell entry and membrane fusion. The SARS-CoV-2 S gene encodes 22 N-linked glycan sequons per protomer, which likely play a role in protein folding and immune evasion. Here, using a site-specific mass spectrometric approach, we reveal the glycan structures on a recombinant SARS-CoV-2 S immunogen. This anal. enables mapping of the glycan-processing states across the trimeric viral spike. We show how SARS-CoV-2 S glycans differ from typical host glycan processing, which may have implications in viral pathobiol. and vaccine design.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhsVSjtLnE&md5=e751e60b601f2c20ff3f1b1d0ef45a3f
  123. 123
    Khan, K. H. DNA Vaccines: Roles against Diseases. GERMS 2013, 3, 26– 35,  DOI: 10.11599/germs.2013.1034
    Google Scholar
    123
    DNA vaccines: roles against diseases
    Khan, Kishwar Hayat
    GERMS (2013), 3 (1), 26-35CODEN: GERMCF; ISSN:2248-2997. (European Academy of HIV/AIDS and Infectious Diseases)
    A review. Vaccination is the most successful application of immunol. principles to human health. Vaccine efficacy needs to be reviewed from time to time and its safety is an overriding consideration. DNA vaccines offer simple yet effective means of inducing broad-based immunity. These vaccines work by allowing the expression of the microbial antigen inside host cells that take up the plasmid. These vaccines function by generating the desired antigen inside the cells, with the advantage that this may facilitate presentation through the major histocompatibility complex. This review article is based on a literature survey and it describes the working and designing strategies of DNA vaccines. Advantages and disadvantages for this type of vaccines have also been explained, together with applications of DNA vaccines. DNA vaccines against cancer, tuberculosis, Edwardsiella tarda, HIV, anthrax, influenza, malaria, dengue, typhoid and other diseases were explored.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXnsVCht7o%253D&md5=a3c61bd65fa88affbda37334047465e0
  124. 124
    Alarcon, J. B.; Waine, G. W.; McManus, D. P. DNA Vaccines: Technology and Application as Anti-Parasite and Anti-Microbial Agents. Adv. Parasitol. 1999, 42, 343– 410,  DOI: 10.1016/S0065-308X(08)60152-9
    Google Scholar
    124
    DNA vaccines: technology and application as anti-parasite and anti-microbial agents
    Alarcon J B; Waine G W; McManus D P
    Advances in parasitology (1999), 42 (), 343-410 ISSN:0065-308X.
    DNA vaccines have been termed The Third Generation of Vaccines. The recent successful immunization of experimental animals against a range of infectious agents and several tumour models of disease with plasmid DNA testifies to the powerful nature of this revolutionary approach in vaccinology. Among numerous advantages, a major attraction of DNA vaccines over conventional vaccines is that they are able to induce protective cytotoxic T-cell responses as well as helper T-cell and humoral immunity. Here we review the current state of nucleic acid vaccines and cover a wide range of topics including delivery mechanisms, uptake and expression of plasmid DNA, and the types of immune responses generated. Further, we discuss safety issues, and document the use of nucleic acid vaccines against viral, bacterial and parasitic diseases, and cancer. The early potential promise of DNA vaccination has been fully substantiated with recent, exciting developments including the movement from testing DNA vaccines in laboratory models to non-human primates and initial human clinical trials. These advances and the emerging voluminous literature on DNA vaccines highlight the rapid progress that has been made in the DNA immunization field. It will be of considerable interest to see whether the progress and optimism currently prevailing can be maintained, and whether the approach can indeed fulfil the medical and commerical promise anticipated.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADyaK1M7lvFWrsQ%253D%253D&md5=3be15a1d0595e7d6b099df240e595c5e
  125. 125
    Geall, A. J.; Verma, A.; Otten, G. R.; Shaw, C. A.; Hekele, A.; Banerjee, K.; Cu, Y.; Beard, C. W.; Brito, L. A.; Krucker, T.; O’Hagan, D. T.; Singh, M.; Mason, P. W.; Valiante, N. M.; Dormitzer, P. R.; Barnett, S. W.; Rappuoli, R.; Ulmer, J. B.; Mandl, C. W. Nonviral Delivery of Self-Amplifying RNA Vaccines. Proc. Natl. Acad. Sci. U. S. A. 2012, 109, 14604– 14609,  DOI: 10.1073/pnas.1209367109
    Google Scholar
    125
    Nonviral delivery of self-amplifying RNA vaccines
    Geall, Andrew J.; Verma, Ayush; Otten, Gillis R.; Shaw, Christine A.; Hekele, Armin; Banerjee, Kaustuv; Cu, Yen; Beard, Clayton W.; Brito, Luis A.; Krucker, Thomas; O'Hagan, Derek T.; Singh, Manmohan; Mason, Peter W.; Valiante, Nicholas M.; Dormitzer, Philip R.; Barnett, Susan W.; Rappuoli, Rino; Ulmer, Jeffrey B.; Mandl, Christian W.
    Proceedings of the National Academy of Sciences of the United States of America (2012), 109 (36), 14604-14609, S14604/1-S14604/7CODEN: PNASA6; ISSN:0027-8424. (National Academy of Sciences)
    Despite more than two decades of research and development on nucleic acid vaccines, there is still no com. product for human use. Taking advantage of the recent innovations in systemic delivery of short interfering RNA (siRNA) using lipid nanoparticles (LNPs), we developed a self-amplifying RNA vaccine. Here we show that nonviral delivery of a 9-kb self-amplifying RNA encapsulated within an LNP substantially increased immunogenicity compared with delivery of unformulated RNA. This unique vaccine technol. was found to elicit broad, potent, and protective immune responses, that were comparable to a viral delivery technol., but without the inherent limitations of viral vectors. Given the many pos. attributes of nucleic acid vaccines, our results suggest that a comprehensive evaluation of nonviral technologies to deliver self-amplifying RNA vaccines is warranted.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhsVaqu7zI&md5=2a9e33500776ed4b5db9c1dd4a3ab183
  126. 126
    Kirkpatrick, D. D. U.K. Lab to Sidestep Drug Industry to Sell Potential Virus Vaccine. New York Times Jun 7, 2020.
    Google Scholar
    There is no corresponding record for this reference.
  127. 127
    Petsch, B.; Schnee, M.; Vogel, A. B.; Lange, E.; Hoffmann, B.; Voss, D.; Schlake, T.; Thess, A.; Kallen, K.-J.; Stitz, L.; Kramps, T. Protective Efficacy of in Vitro Synthesized, Specific MRNA Vaccines against Influenza A Virus Infection. Nat. Biotechnol. 2012, 30, 1210– 1216,  DOI: 10.1038/nbt.2436
    Google Scholar
    127
    Protective efficacy of in vitro synthesized, specific mRNA vaccines against influenza A virus infection
    Petsch, Benjamin; Schnee, Margit; Vogel, Annette B.; Lange, Elke; Hoffmann, Bernd; Voss, Daniel; Schlake, Thomas; Thess, Andreas; Kallen, Karl-Josef; Stitz, Lothar; Kramps, Thomas
    Nature Biotechnology (2012), 30 (12), 1210-1216CODEN: NABIF9; ISSN:1087-0156. (Nature Publishing Group)
    Despite substantial improvements, influenza vaccine prodn.-and availability-remain suboptimal. Influenza vaccines based on mRNA may offer a soln. as sequence-matched, clin.-grade material could be produced reliably and rapidly in a scalable process, allowing quick response to the emergence of pandemic strains. Here we show that mRNA vaccines induce balanced, long-lived and protective immunity to influenza A virus infections in even very young and very old mice and that the vaccine remains protective upon thermal stress. This vaccine format elicits B and T cell-dependent protection and targets multiple antigens, including the highly conserved viral nucleoprotein, indicating its usefulness as a cross-protective vaccine. In ferrets and pigs, mRNA vaccines induce immunol. correlates of protection and protective effects similar to those of a licensed influenza vaccine in pigs. Thus, mRNA vaccines could address substantial medical need in the area of influenza prophylaxis and the broader realm of anti-infective vaccinol.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38Xhs1ymsbjO&md5=11dd1307065ed07df9ea1f009d7d484c
  128. 128
    Fotin-Mleczek, M.; Duchardt, K. M.; Lorenz, C.; Pfeiffer, R.; Ojkic-Zrna, S.; Probst, J.; Kallen, K.-J. Messenger RNA-Based Vaccines With Dual Activity Induce Balanced TLR-7 Dependent Adaptive Immune Responses and Provide Antitumor Activity. J. Immunother. 2011, 34, 1– 15,  DOI: 10.1097/CJI.0b013e3181f7dbe8
    Google Scholar
    128
    Messenger RNA-based vaccines with dual activity induce balanced TLR-7 dependent adaptive immune responses and provide antitumor activity
    Fotin-Mleczek Mariola; Duchardt Katharina M; Lorenz Christina; Pfeiffer Regina; Ojkic-Zrna Sanja; Probst Jochen; Kallen Karl-Josef
    Journal of immunotherapy (Hagerstown, Md. : 1997) (2011), 34 (1), 1-15 ISSN:.
    Direct vaccination with messenger RNA (mRNA) molecules encoding tumor-associated antigens is a novel and promising approach in cancer immunotherapy. The main advantage of using mRNA for vaccination is that the same molecule not only provides an antigen source for adaptive immunity, but can simultaneously bind to pattern recognition receptors, thus stimulating innate immunity. However, achieving both features remains challenging, as the complexation of mRNA required for immune-stimulating activity may inhibit its translatability. In this study, we present a new and more effective vaccine design: a two-component mRNA-based tumor vaccine that supports both: antigen expression and immune stimulation, mediated by Toll like receptor 7 (TLR7). The two-component mRNA vaccines, containing free and protamine-complexed mRNA, induce balanced adaptive immune responses providing humoral as well as T cell mediated immunity. This balanced immune response is based on the induction of antigen-specific CD4(+) T helper cells and cytotoxic CD8(+) T cells. Once activated, these CD4(+) and CD8(+) T cells secrete a wide set of cytokines, which drive a TH1 response. Immunization with the two-component vaccines induces sustained memory responses, mediated by antigen-specific memory T cells. Moreover, treatment of mice with the two-component mRNA vaccine mediates a strong antitumor response against OVA-expressing tumor cells, not only in a prophylactic but also in a therapeutic setting. In conclusion, two-component mRNA vaccines with self-adjuvanting activity induce balanced adaptive immune responses and mediate sustained antitumor activity.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC3M%252FktFGntA%253D%253D&md5=8fea4b31d8126e34caeb4c30a3e91ce0
  129. 129
    Bangari, D. S.; Mittal, S. K. Development of Nonhuman Adenoviruses as Vaccine Vectors. Vaccine 2006, 24, 849– 862,  DOI: 10.1016/j.vaccine.2005.08.101
    Google Scholar
    129
    Development of nonhuman adenoviruses as vaccine vectors
    Bangari, Dinesh S.; Mittal, Suresh K.
    Vaccine (2006), 24 (7), 849-862CODEN: VACCDE; ISSN:0264-410X. (Elsevier B.V.)
    A review. Human adenoviral (HAd) vectors have demonstrated great potential as vaccine vectors. Preclin. and clin. studies have demonstrated the feasibility of vector design, robust antigen expression and protective immunity using this system. However, clin. use of adenoviral vectors for vaccine purposes is anticipated to be limited by vector immunity that is either preexisting or develops rapidly following the first inoculation with adenoviral vectors. Vector immunity inactivates the vector particles and rapidly removes the transduced cells, thereby limiting the duration of transgene expression. Due to strong vector immunity, subsequent use of the same vector is usually less efficient. In order to circumvent this limitation, nonhuman adenoviral vectors have been proposed as alternative vectors. In addn. to eluding HAd immunity, these vectors possess most of the attractive features of HAd vectors. Several replication-competent or replication-defective nonhuman adenoviral vectors have been developed and investigated for their potential as vaccine-delivery vectors. Here, we review recent advances in the design and characterization of various nonhuman adenoviral vectors, and discuss their potential applications for human and animal vaccination.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD28Xhtleit7k%253D&md5=7d3e1591d789b682fe413269adad4b38
  130. 130
    Crawford-Miksza, L.; Schnurr, D. P. Analysis of 15 Adenovirus Hexon Proteins Reveals the Location and Structure of Seven Hypervariable Regions Containing Serotype-Specific Residues. J. Virol. 1996, 70, 1836– 1844,  DOI: 10.1128/JVI.70.3.1836-1844.1996
    Google Scholar
    130
    Analysis of 15 adenovirus hexon proteins reveals the location and structure of seven hypervariable regions containing serotype-specific residues
    Crawford-Miksza, Leta; Schnurr, David P.
    Journal of Virology (1996), 70 (3), 1836-44CODEN: JOVIAM; ISSN:0022-538X. (American Society for Microbiology)
    The first full-length hexon protein DNA and deduced amino acid sequences of a subgenus D adenovirus (AV) were detd. from candidate AV48 (85-0844). Comprehensive comparison of this sequence with hexon protein sequences from human subgenera A, B, C, D, F, bovine AV3, and mouse AV1 revealed seven discrete hypervariable regions (HVRs) among the 250 variable residues in loops 1 and 2. These regions differed in length between serotypes, from 2 to 38 residues, and contained >99% of hexon serotype-specific residues among human serotypes. Alignment with the published crystal structure of AV2 established the location and structure of the type-specific regions. Five HVRs were shown to be part of linear loops on the exposed surfaces of the protein, analogous to the serotype-specific loops or "puffs" in picornavirus capsid proteins. The HVRs were supported by a common framework of conserved residues, of which 68 to 75% were hydrophobic. Unique sequences were limited to the seven HVRs, so that one or more of these regions contain the type-specific neutralization epitopes. A neutralizing AV48 hexon-specific antiserum recognized linear peptides that corresponded to six HVRs by enzyme immunoassay. Affinity-purifn. removal of all peptide-reactive antibodies did not significantly decrease the neutralization titer. Eluted peptide-reactive antibodies did not neutralize. Human antisera that neutralized AV48 did not recognize linear peptides. Purified trimeric native hexon inhibited neutralization, but monomeric heat-denatured hexon did not. We conclude that the AV48 neutralization epitope(s) is complex and conformational.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK28XpvFaktg%253D%253D&md5=e5cb61f4a392ec45b3f42f5a1801206b
  131. 131
    Baxi, M. K.; Deregt, D.; Robertson, J.; Babiuk, L. A.; Schlapp, T.; Tikoo, S. K. Recombinant Bovine Adenovirus Type 3 Expressing Bovine Viral Diarrhea Virus Glycoprotein E2 Induces an Immune Response in Cotton Rats. Virology 2000, 278, 234– 243,  DOI: 10.1006/viro.2000.0661
    Google Scholar
    131
    Recombinant Bovine Adenovirus Type 3 Expressing Bovine Viral Diarrhea Virus Glycoprotein E2 Induces an Immune Response in Cotton Rats
    Baxi, Mohit K.; Deregt, Dirk; Robertson, Jill; Babiuk, Lorne A.; Schlapp, Tobias; Tikoo, Suresh K.
    Virology (2000), 278 (1), 234-243CODEN: VIRLAX; ISSN:0042-6822. (Academic Press)
    Recombinant bovine adenovirus is being developed as a live vector for animal vaccination and for human gene therapy. In this study, two replication-competent bovine adenovirus 3 (BAV-3) recombinants (BAV331 and BAV338) expressing bovine viral diarrhea virus (BVDV) glycoprotein E2 in the early region 3 (E3) of BAV-3 were constructed. Recombinant BAV331 contains chem. synthesized E2 gene (nucleotides modified to remove internal cryptic splice sites) under the control of BAV-3 E3/major late promoter (MLP), while recombinant BAV338 contains original E2 gene under the control of human cytomegalovirus immediate early promoter. Since E2, a class I membrane glycoprotein, does not contain its own signal peptide sequence at the 5' end, the bovine herpesvirus 1 (BHV-1) glycoprotein D signal sequence was fused in frame to the E2 open reading frame (ORF) for proper processing of the E2 glycoprotein in both the recombinant viruses. Recombinant E2 protein expressed by BAV331 and BAV338 recombinant viruses was recognized by E2-specific monoclonal antibodies as a 53-kDa protein, which also formed dimer with an apparent mol. wt. of 94 kDa. Insertion of an E2-expression cassette in the E3 region did not effect the replication of recombinant BAV-3s. Intranasal immunization of cotton rats with these recombinant viruses generated E2-specific IgA and IgG responses at the mucosal surfaces and in the serum. In summary, these results show that the pestivirus glycoprotein can be expressed efficiently by BAV-3. In addn., mucosal immunization with replication-competent recombinant bovine adenovirus 3 can induce a specific immune response against the expressed antigen. (c) 2000 Academic Press.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3cXosFGns7s%253D&md5=b0a98f1199b3c9543b873b40a4ccb10c
  132. 132
    Fischer, L.; Tronel, J. P.; Pardo-David, C.; Tanner, P.; Colombet, G.; Minke, J.; Audonnet, J.-C. Vaccination of Puppies Born to Immune Dams with a Canine Adenovirus-Based Vaccine Protects against a Canine Distemper Virus Challenge. Vaccine 2002, 20, 3485– 3497,  DOI: 10.1016/S0264-410X(02)00344-4
    Google Scholar
    132
    Vaccination of puppies born to immune dams with a canine adenovirus-based vaccine protects against a canine distemper virus challenge
    Fischer, Laurent; Tronel, Jean Philippe; Pardo-David, Camilla; Tanner, Patrick; Colombet, Guy; Minke, Jules; Audonnet, Jean-Christophe
    Vaccine (2002), 20 (29-30), 3485-3497CODEN: VACCDE; ISSN:0264-410X. (Elsevier Science Ltd.)
    None of the currently available distemper vaccines provides a satisfactory soln. for the immunization of very young carnivores in the face of maternal-derived immunity. Since mucosal immunization with replication-competent adenovirus-based vaccines has been proven effective in the face of passive immunity against the vector, it has the potential to provide a soln. for the vaccination of young puppies born to canine distemper virus (CDV)-immune dams. The authors report the engineering and the characterization of two replication-competent canine adenovirus type 2 (CAV2)-based vaccines expressing, resp., the CDV hemagglutinin (HA) and fusion (F) antigens. The authors first demonstrated that the intranasal vaccination with a mixt. of both recombinant CAV2s provides an excellent level of protection in seroneg. puppies, confirming the value of replication-competent adenovirus-based vectors for mucosal vaccination. In contrast, intranasal immunization with the same vaccine of puppies born to CDV- and CAV2-immune dams, failed to activate specific and protective immune responses. The authors hypothesized that an active CAV2 infection occurred while puppies were in close contact with the vaccinated dams in the breeding units and that the resulting active mucosal immunity interfered with the intranasal administration of CAV2-based CDV vaccine. However, when puppies born to CDV- and CAV2-immune dams were vaccinated s.c. with the CAV2-based CDV vaccine, significant seroconversion and solid protective immunity were triggered despite pre-existing systemic immunity to the vector. This latter result is surprising and suggests that s.c. vaccination with a replication-competent recombinant CAV2 may be an efficient strategy to overcome both passive and active adenovirus specific immunity in the dog. From a practical point of view, this could pave the way for an original strategy to vaccinate young puppies in the face of maternal-derived immunity.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD38Xnt1Crurg%253D&md5=07512a3d42f159ecb3c73e3e57c4b795
  133. 133
    Wüest, T.; Both, G. W.; Prince, A. M.; Hofmann, C.; Löser, P. Recombinant Ovine Atadenovirus Induces a Strong and Sustained T Cell Response against the Hepatitis C Virus NS3 Antigen in Mice. Vaccine 2004, 22, 2717– 2721,  DOI: 10.1016/j.vaccine.2004.01.048
    Google Scholar
    There is no corresponding record for this reference.
  134. 134
    Bangari, D. S.; Mittal, S. K. Porcine Adenoviral Vectors Evade Preexisting Humoral Immunity to Adenoviruses and Efficiently Infect Both Human and Murine Cells in Culture. Virus Res. 2004, 105, 127– 136,  DOI: 10.1016/j.virusres.2004.05.003
    Google Scholar
    134
    Porcine adenoviral vectors evade preexisting humoral immunity to adenoviruses and efficiently infect both human and murine cells in culture
    Bangari, Dinesh S.; Mittal, Suresh K.
    Virus Research (2004), 105 (2), 127-136CODEN: VIREDF; ISSN:0168-1702. (Elsevier B.V.)
    Preexisting immunity against human adenoviruses (HAd) limits the efficiency of transduction of HAd vectors in humans. In addn., development of a vector-specific immune response after the first inoculation with a HAd vector further lowers vector uptake following readministration. The authors investigated the usefulness of porcine adenovirus serotype 3 (PAd3)-based vectors as a supplement to HAd vectors. Here the authors demonstrate that preexisting HAd-specific neutralizing antibodies in humans do not cross-neutralize PAd3. To generate E1A-deleted PAd3 vectors, an E1-complementing cell line of porcine origin was produced. E1A-deleted PAd3 vector expressing green fluorescent protein; GFP (PAd-GFP) and E1-deleted HAd5 vector expressing GFP (HAd-GFP) transduced human cell lines with comparable efficiencies. Both of these vectors efficiently transduced murine MT1A2 breast cancer cell line, while PAd-GFP transduced murine NIH 3T3 fibroblast cell line significantly better than HAd-GFP. These results suggest that PAd3 vectors would be promising supplement to HAd vectors as a delivery vehicle for recombinant vaccines and gene therapy applications.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2cXntlSmtLs%253D&md5=7d8313d9cdb45ba7ea86d191d4479ec7
  135. 135
    Rasmussen, U. B.; Benchaibi, M.; Meyer, V.; Schlesinger, Y.; Schughart, K. Novel Human Gene Transfer Vectors: Evaluation of Wild-Type and Recombinant Animal Adenoviruses in Human-Derived Cells. Hum. Gene Ther. 1999, 10, 2587– 2599,  DOI: 10.1089/10430349950016636
    Google Scholar
    135
    Novel human gene transfer vectors: evaluation of wild-type and recombinant animal adenoviruses in human-derived cells
    Rasmussen, Ulla B.; Benchaibi, Miloud; Meyer, Veronique; Schlesinger, Yasmin; Schughart, Klaus
    Human Gene Therapy (1999), 10 (16), 2587-2599CODEN: HGTHE3; ISSN:1043-0342. (Mary Ann Liebert, Inc.)
    Major disadvantages of human adenovirus (hAd) vectors in gene therapy include preexisting or induced immune responses, and possible coreplication of recombinant hAd in the presence of wild-type hAds. These disadvantages may be overcome by using nonhuman, animal adenoviruses (aAds). We evaluated four different aAds for their potential use as viral vectors. The canine adenovirus type 2 (CAV2) and bovine adenovirus type 3 (BAV3) appeared to be suitable systems, as they infect human cells. CAV2, but not BAV3, caused cytotoxicity, and only limited (CAV2) or no (BAV3) prodn. of infectious virus particles was obsd. after infection of human cell lines. CAV2 showed higher expression of endogenous genes than did BAV3 in the tested human cells. No interference between hAd and CAV2 or BAV3, such as recombination of DNA or cross-activation of virus replication, was obsd. in up to five passages in double-infected human cells. Transfection of cloned genomic CAV2 or BAV3 DNA into appropriate permissive cell lines rescued infectious virus. Furthermore, we produced a recombinant E1-deleted BAV3, and showed that it could infect and express a reporter gene in various human cell types.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK1MXnt1yrsL8%253D&md5=97881cc59c410700f3dd866f158ffbff
  136. 136
    Bangari, D. S.; Shukla, S.; Mittal, S. K. Comparative Transduction Efficiencies of Human and Nonhuman Adenoviral Vectors in Human, Murine, Bovine, and Porcine Cells in Culture. Biochem. Biophys. Res. Commun. 2005, 327, 960– 966,  DOI: 10.1016/j.bbrc.2004.12.099
    Google Scholar
    136
    Comparative transduction efficiencies of human and nonhuman adenoviral vectors in human, murine, bovine, and porcine cells in culture
    Bangari, Dinesh S.; Shukla, Shruti; Mittal, Suresh K.
    Biochemical and Biophysical Research Communications (2005), 327 (3), 960-966CODEN: BBRCA9; ISSN:0006-291X. (Elsevier)
    Clin. usefulness of human Ad serotype 5 (HAd5) based vectors is limited primarily because of preexisting Ad immunity and lack of targeting to specific cell types. Alternative vectors based on less prevalent HAd serotypes as well as nonhuman adenoviruses such as porcine Ad serotype 3 (PAd3) and bovine Ad serotype 3 (BAd3) are being developed to overcome these shortcomings. Using virus neutralization assay, the authors examd. whether preexisting Ad immunity in humans would cross-neutralize PAd3 or BAd3. To further evaluate the potential of PAd3 and BAd3 vectors as gene delivery vehicles, we compared their transduction efficiencies in a panel of human, murine, bovine, and porcine cell lines to those obtained with a HAd5 vector. Transduction by the HAd5 vector in the majority of human cell lines correlated with the expression levels of coxsackievirus-adenovirus receptor (CAR), the primary HAd5 receptor; while transduction by PAd3 and BAd3 vectors was CAR-independent. The results suggest that PAd3 and BAd3 vectors are promising gene delivery vehicles for human gene therapy as well as for recombinant vaccines for human and animal use.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2MXksFGhtA%253D%253D&md5=571572a1ecfd5904257da7761ca83127
  137. 137
    Kümin, D.; Hofmann, C.; Rudolph, M.; Both, G. W.; Löser, P. Biology of Ovine Adenovirus Infection of Nonpermissive Cells. J. Virol. 2002, 76, 10882– 10893,  DOI: 10.1128/JVI.76.21.10882-10893.2002
    Google Scholar
    There is no corresponding record for this reference.
  138. 138
    Sinovac Says Its Covid-19 Vaccine Generated Immune Responses. STAT , 2020.
    Google Scholar
    There is no corresponding record for this reference.
  139. 139
    China’s Sinopharm Touts 100% Antibody Response for COVID-19 Vaccine It’s Already Giving to Workers. https://www.fiercepharma.com/pharma-asia/china-s-sinopharm-touts-100-antibody-response-for-covid-19-vaccine-it-s-already-giving (accessed 2020-07-27).
    Google Scholar
    There is no corresponding record for this reference.
  140. 140
    Chinese Researchers Launch Phase-2 Human Test for Possible Coronavirus Vaccine. Reuters Jun 21, 2020.
    Google Scholar
    There is no corresponding record for this reference.
  141. 141
    Zydus to Start Second Phase of Covid-19 Vaccine Candidate Trials Today. https://www.hindustantimes.com/india-news/zydus-to-start-second-phase-of-vaccine-candidate-trials-today/story-AkiC1iDUI9azdTSVbDFOQM.html (accessed 2020-08-10).
    Google Scholar
    There is no corresponding record for this reference.
  142. 142
    Keech, C.; Albert, G.; Cho, I.; Robertson, A.; Reed, P.; Neal, S.; Plested, J. S.; Zhu, M.; Cloney-Clark, S.; Zhou, H.; Smith, G.; Patel, N.; Frieman, M. B.; Haupt, R. E.; Logue, J.; McGrath, M.; Weston, S.; Piedra, P. A.; Desai, C.; Callahan, K. Phase 1–2 Trial of a SARS-CoV-2 Recombinant Spike Protein Nanoparticle Vaccine. N. Engl. J. Med. 2020, 0 (0), null,  DOI: 10.1056/NEJMoa2026920
    Google Scholar
    There is no corresponding record for this reference.
  143. 143
    Corum, J.; Grady, D.; Wee, S.-L.; Zimmer, C. Coronavirus Vaccine Tracker. New York Times , 2020.
    Google Scholar
    There is no corresponding record for this reference.
  144. 144
    Putin Announces First “Registered” COVID-19 Vaccine from Russia’s Gamaleya Institute; His Daughter among Those Inoculated - Health News, Firstpost. https://www.firstpost.com/health/putin-announces-first-registered-covid-19-vaccine-from-russias-gamaleya-institute-his-daughter-among-those-inoculated-8695031.html (accessed 2020-08-14).
    Google Scholar
    There is no corresponding record for this reference.
  145. 145
    Putin Says Russia has Approved “World First” Covid-19 Vaccine. But Questions Over Its Safety Remain. https://www.cnn.com/2020/08/11/europe/russia-coronavirus-vaccine-putin-intl/index.html (accessed 2020-08-14).
    Google Scholar
    There is no corresponding record for this reference.
  146. 146
    Hayashi, M.; Aoshi, T.; Haseda, Y.; Kobiyama, K.; Wijaya, E.; Nakatsu, N.; Igarashi, Y.; Standley, D. M.; Yamada, H.; Honda-Okubo, Y.; Hara, H.; Saito, T.; Takai, T.; Coban, C.; Petrovsky, N.; Ishii, K. J. Advax, a Delta Inulin Microparticle, Potentiates In-Built Adjuvant Property of Co-Administered Vaccines. EBioMedicine 2017, 15, 127– 136,  DOI: 10.1016/j.ebiom.2016.11.015
    Google Scholar
    146
    Advax, a Delta Inulin Microparticle, Potentiates In-built Adjuvant Property of Co-administered Vaccines
    Hayashi Masayuki; Aoshi Taiki; Haseda Yasunari; Kobiyama Kouji; Wijaya Edward; Standley Daron M; Nakatsu Noriyuki; Igarashi Yoshinobu; Yamada Hiroshi; Honda-Okubo Yoshikazu; Hara Hiromitsu; Saito Takashi; Takai Toshiyuki; Coban Cevayir; Petrovsky Nikolai; Ishii Ken J
    EBioMedicine (2017), 15 (), 127-136 ISSN:.
    Advax, a delta inulin-derived microparticle, has been developed as an adjuvant for several vaccines. However, its immunological characteristics and potential mechanism of action are yet to be elucidated. Here, we show that Advax behaves as a type-2 adjuvant when combined with influenza split vaccine, a T helper (Th)2-type antigen, but behaves as a type-1 adjuvant when combined with influenza inactivated whole virion (WV), a Th1-type antigen. In addition, an adjuvant effect was not observed when Advax-adjuvanted WV vaccine was used to immunize toll-like receptor (TLR) 7 knockout mice which are unable to respond to RNA contained in WV antigen. Similarly, no adjuvant effect was seen when Advax was combined with endotoxin-free ovalbumin, a neutral Th0-type antigen. An adjuvant effect was also not seen in tumor necrosis factor (TNF)-α knockout mice, and the adjuvant effect required the presences of dendritic cells (DCs) and phagocytic macrophages. Therefore, unlike other adjuvants, Advax potentiates the intrinsic or in-built adjuvant property of co-administered antigens. Hence, Advax is a unique class of adjuvant which can potentiate the intrinsic adjuvant feature of the vaccine antigens through a yet to be determined mechanism.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2sjjs12qtQ%253D%253D&md5=7af63ca16d7fc8389d93f22be67d7235
  147. 147
    Calcagnile, S.; Zuccotti, G. V. The Virosomal Adjuvanted Influenza Vaccine. Expert Opin. Biol. Ther. 2010, 10, 191– 200,  DOI: 10.1517/14712590903431014
    Google Scholar
    147
    The virosomal adjuvanted influenza vaccine
    Calcagnile Selma; Zuccotti Gian Vincenzo
    Expert opinion on biological therapy (2010), 10 (2), 191-200 ISSN:.
    IMPORTANCE OF THE FIELD: The protection conferred by influenza vaccines varies for several reasons, for example the age or degree of immune depression of the recipient. All currently available seasonal influenza vaccines are safe and substantially effective in preventing influenza in healthy people. However, elderly people and patients with chronic diseases or immune system defects need a more effective vaccine to avoid serious risks from influenza and its complications. Research has been undertaken to improve the efficacy of vaccination. Recent research includes the use of new adjuvants or antigen-presenting strategies. AREAS COVERED IN THIS REVIEW: The virosomal adjuvanted subunit influenza vaccine has been studied in groups for whom vaccination is recommended. We describe virosomal technology, including production and mode of action, as well as the available efficacy, immunogenicity and safety data, with the aim of understanding the benefits of this vaccine's use. WHAT THE READER WILL GAIN: A review of published data on efficacy, immunogenicity and safety from sponsor- and investigator- driven studies, focusing on recent publications. TAKE HOME MESSAGE: The vaccine was generally very immunogenic and safe in all investigated populations. Its ability to induce protective antibody titers has been shown to exceed that of conventional influenza vaccines in elderly people and individuals with little or no prior exposure to the viral strains.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC3c%252FksF2nsA%253D%253D&md5=1daeb8908c974e688026873457e471fa
  148. 148
    Garçon, N.; Vaughn, D. W.; Didierlaurent, A. M. Development and Evaluation of AS03, an Adjuvant System Containing α-Tocopherol and Squalene in an Oil-in-Water Emulsion. Expert Rev. Vaccines 2012, 11, 349– 366,  DOI: 10.1586/erv.11.192
    Google Scholar
    148
    Development and evaluation of AS03, an Adjuvant System containing αα-tocopherol and squalene in an oil-in-water emulsion
    Garcon, Nathalie; Vaughn, David W.; Didierlaurent, Arnaud M.
    Expert Review of Vaccines (2012), 11 (3), 349-366CODEN: ERVXAX; ISSN:1476-0584. (Expert Reviews Ltd.)
    A review. AS03 is an Adjuvant System composed of αα-tocopherol, squalene and polysorbate 80 in an oil-in-water emulsion. In various nonclin. and clin. studies, high levels of antigen-specific antibodies were obtained after administration of an AS03-adjuvanted vaccine, permitting antigen-sparing strategies. AS03 has been shown to enhance the vaccine antigen-specific adaptive response by activating the innate immune system locally and by increasing antigen uptake and presentation in draining lymph nodes, a process that is modulated by the presence of αα-tocopherol in AS03. In nonclin. models of the AS03-adjuvanted prepandemic H5N1 influenza vaccine, increased levels of anti-influenza antibody afforded protection against disease and against virus replication of influenza strains homologous and heterologous to the vaccine strain. By incorporating AS03 in the pandemic H1N1/2009 vaccine, vaccine immunogenicity was increased compared with nonadjuvanted H1N1 vaccines. High H1N1/2009/AS03 vaccine effectiveness was demonstrated in several assessments in multiple populations. Altogether, the nonclin. and clin. data illustrate the ability of AS03 to induce superior adaptive responses against the vaccine antigen, principally in terms of antibody levels and immune memory. In general, these results support the concept of Adjuvant Systems as a plausible approach to develop new effective vaccines.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XjtlOjtLY%253D&md5=3736be68e96e9e37d3aa7c5733a5b23d
  149. 149
    A Phase 1, Randomized, Double-Blind, Placebo-Controlled, First-in-Human Study to Evaluate the Safety and Immunogenicity of SCB 2019, a Recombinant SARS-CoV-2 Trimeric S Protein Subunit Vaccine for COVID-19 in Healthy Volunteers - Full Text View. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT04405908 (accessed 2020-08-03).
    Google Scholar
    There is no corresponding record for this reference.
  150. 150
    A Randomized, Partially-Blinded, Dose-Ranging Phase 1 Study to Assess the Safety, Tolerability, and Immunogenicity of a Recombinant Coronavirus-Like Particle COVID 19 Vaccine in Adults 18–55 Years of Age - Full Text View. ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT04450004 (accessed 2020-08-03).
    Google Scholar
    There is no corresponding record for this reference.
  151. 151
    Sanofi: Press Releases, Tuesday, April 14, 2020. https://www.sanofi.com/media-room/press-releases/2020/2020-04-14 13–00–00 2015521 (accessed 2020-08-03).
    Google Scholar
    There is no corresponding record for this reference.
  152. 152
    GSK Allies with Innovax for COVID-19 Vaccine R&D Project. https://www.fiercebiotech.com/biotech/gsk-allies-innovax-for-covid-19-vaccine-r-d-project (accessed 2020-04-09).
    Google Scholar
    There is no corresponding record for this reference.
  153. 153
    GSK Makes Adjuvant Available to Coronavirus Vaccine Project. https://www.fiercebiotech.com/biotech/gsk-makes-adjuvant-available-to-coronavirus-vaccine-project (accessed 2020-08-03).
    Google Scholar
    There is no corresponding record for this reference.
  154. 154
    Campbell, J. D. Development of the CpG Adjuvant 1018: A Case Study. Methods Mol. Biol. 2017, 1494, 15– 27,  DOI: 10.1007/978-1-4939-6445-1_2
    Google Scholar
    154
    Development of the CpG adjuvant 1018: a case study
    Campbell, John D.
    Methods in Molecular Biology (New York, NY, United States) (2017), 1494 (Vaccine Adjuvants), 15-27CODEN: MMBIED; ISSN:1940-6029. (Springer)
    The development of aluminum salts (alum) as vaccine adjuvants was an empirical process with little understanding of the mechanism of action and, with decades of use, it has become clear that there is a need for alternatives where alum-based adjuvants are suboptimal. Oligonucleotides contg. unmethylated CpG sequences represent one alternative as they are potent stimulators of the vertebrate innate immune system through activation of Toll-like receptor-9. This chapter outlines the methods used by Dynavax Technologies to progress a CpG-contg. oligonucleotide sequence termed 1018 through preclin. and clin. testing as an adjuvant for immunization against hepatitis B virus (HBV). 1018 Is a short (22-mer) oligonucleotide sequence contg. CpG motifs active in both rodents and primates. Preclin. testing of hepatitis B surface antigen (HBsAg) + 1018 in comparison to HBsAg + alum demonstrated induction of substantially higher antibody titers and a favorable safety profile for 1018. Most importantly, clin. studies with HBsAg vaccination consistently demonstrate more rapid induction of protective antibody titers with 1018 compared to alum in all populations studied, including groups that are harder to immunize such as the elderly and immunocompromised individuals. These studies represent the basis for use of the CpG-motif-contg. oligonucleotide 1018 as an improved adjuvant for HBsAg immunogenicity. HBsAg + 1018 (HEPLISAV-B ) is currently in late-stage clin. testing for prophylactic immunization against HBV.
    >> More from SciFinder ®
    https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhvFWisLvM&md5=bd1b425b5696f78ad5e937544062bf9a
  155. 155
    A Phase I, Prospective, Open-Labeled Study to Evaluate the Safety and Immunogenicity of MVC-COV1901 - Full Text View. ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT04487210 (accessed 2020-08-03).
    Google Scholar
    There is no corresponding record for this reference.
  156. 156
    Dynavax and Sinovac Announce Collaboration to Develop a Coronavirus (COVID-19) Vaccine. Dynavax Technologies Corp.https://investors.dynavax.com/news-releases/news-release-details/dynavax-and-sinovac-announce-collaboration-develop-coronavirus (accessed 2020-08-03).
    Google Scholar
    There is no corresponding record for this reference.
  157. 157
    Valneva and Dynavax Announce Collaboration to Advance Vaccine Development for COVID-19. Valneva. https://valneva.com/press-release/valneva-and-dynavax-announce-collaboration-to-advance-vaccine-development-for-covid-19/ (accessed 2020-08-03).
    Google Scholar
    There is no corresponding record for this reference.

Cited By

ARTICLE SECTIONS
Jump To

This article is cited by 247 publications.

  1. Pierre Picchetti, Stefano Volpi, Marianna Rossetti, Michael D. Dore, Tuan Trinh, Frank Biedermann, Martina Neri, Alessandro Bertucci, Alessandro Porchetta, Roberto Corradini, Hanadi Sleiman, Luisa De Cola. Responsive Nucleic Acid-Based Organosilica Nanoparticles. Journal of the American Chemical Society 2023, 145 (42) , 22896-22902. https://doi.org/10.1021/jacs.3c00393
  2. Ceri J. Richards, Thomas C. Q. Burgers, Rifka Vlijm, Wouter H. Roos, Christoffer Åberg. Rapid Internalization of Nanoparticles by Human Cells at the Single Particle Level. ACS Nano 2023, 17 (17) , 16517-16529. https://doi.org/10.1021/acsnano.3c01124
  3. Xin Wang, Jimei Wu, Zhiguang Zhang, Guirong Xiong. Surfactant-Tunable Nanoparticle Assembly via a Template-Directed Strategy. Langmuir 2023, 39 (16) , 5825-5832. https://doi.org/10.1021/acs.langmuir.3c00116
  4. Young Hun Chung, Britney A. Volckaert, Nicole F. Steinmetz. Development of a Modular NTA:His Tag Viral Vaccine for Co-delivery of Antigen and Adjuvant. Bioconjugate Chemistry 2023, 34 (1) , 269-278. https://doi.org/10.1021/acs.bioconjchem.2c00601
  5. Anooshay Khan, Julian Ostaku, Ebru Aras, Urartu Ozgur Safak Seker. Combating Infectious Diseases with Synthetic Biology. ACS Synthetic Biology 2022, 11 (2) , 528-537. https://doi.org/10.1021/acssynbio.1c00576
  6. Natalie Boehnke, Paula T. Hammond. Power in Numbers: Harnessing Combinatorial and Integrated Screens to Advance Nanomedicine. JACS Au 2022, 2 (1) , 12-21. https://doi.org/10.1021/jacsau.1c00313
  7. Jiafeng Pan, Ying He, Zhi Liu, Junhua Chen. Tetrahedron-Based Constitutional Dynamic Network for COVID-19 or Other Coronaviruses Diagnostics and Its Logic Gate Applications. Analytical Chemistry 2022, 94 (2) , 714-722. https://doi.org/10.1021/acs.analchem.1c03051
  8. Lisa Pokrajac, Ali Abbas, Wojciech Chrzanowski, Goretty M. Dias, Benjamin J. Eggleton, Steven Maguire, Elicia Maine, Timothy Malloy, Jatin Nathwani, Linda Nazar, Adrienne Sips, Jun’ichi Sone, Albert van den Berg, Paul S. Weiss, Sushanta Mitra. Nanotechnology for a Sustainable Future: Addressing Global Challenges with the International Network4Sustainable Nanotechnology. ACS Nano 2021, 15 (12) , 18608-18623. https://doi.org/10.1021/acsnano.1c10919
  9. Bebeto Rai, Robert Malmberg, Venkatesh Srinivasan, Kalathur Mohan Ganesh, Naga Sai Visweswar Kambhampati, Abhay Andar, Govind Rao, Carani B. Sanjeevi, Koushik Venkatesan, Sai Sathish Ramamurthy. Surface Plasmon-Coupled Dual Emission Platform for Ultrafast Oxygen Monitoring after SARS-CoV-2 Infection. ACS Sensors 2021, 6 (12) , 4360-4368. https://doi.org/10.1021/acssensors.1c01665
  10. Morgan Chandler, Brittany Johnson, Emil Khisamutdinov, Marina A. Dobrovolskaia, Joanna Sztuba-Solinska, Aliasger K. Salem, Koen Breyne, Roger Chammas, Nils G. Walter, Lydia M. Contreras, Peixuan Guo, Kirill A. Afonin. The International Society of RNA Nanotechnology and Nanomedicine (ISRNN): The Present and Future of the Burgeoning Field. ACS Nano 2021, 15 (11) , 16957-16973. https://doi.org/10.1021/acsnano.0c10240
  11. Wolfgang J. Parak, (Associate Editor)Tanja Weil, (Editorial Advisory Board and Associate Editor of the Journal of the American Chemical Society)Paul S. Weiss (Editor-in-Chief). A Virtual Issue on Nanomedicine. ACS Nano 2021, 15 (10) , 15397-15401. https://doi.org/10.1021/acsnano.1c09106
  12. Oscar A. Ortega-Rivera, Matthew D. Shin, Angela Chen, Veronique Beiss, Miguel A. Moreno-Gonzalez, Miguel A. Lopez-Ramirez, Maria Reynoso, Hong Wang, Brett L. Hurst, Joseph Wang, Jonathan K. Pokorski, Nicole F. Steinmetz. Trivalent Subunit Vaccine Candidates for COVID-19 and Their Delivery Devices. Journal of the American Chemical Society 2021, 143 (36) , 14748-14765. https://doi.org/10.1021/jacs.1c06600
  13. Sameera Wickramasinghe, Jingxin Wang, Badie Morsi, Bingyun Li. Carbon Dioxide Conversion to Nanomaterials: Methods, Applications, and Challenges. Energy & Fuels 2021, 35 (15) , 11820-11834. https://doi.org/10.1021/acs.energyfuels.1c01533
  14. Paul S. Weiss (Editor-in-Chief). Touting the Growing Contributions of Nanoscience and Nanotechnology. ACS Nano 2021, 15 (7) , 10737-10738. https://doi.org/10.1021/acsnano.1c05996
  15. Laura Talamini, Pierre Picchetti, Lorena Maria Ferreira, Giovanni Sitia, Luca Russo, Martina B. Violatto, Leana Travaglini, Jennifer Fernandez Alarcon, Lucrezia Righelli, Paolo Bigini, Luisa De Cola. Organosilica Cages Target Hepatic Sinusoidal Endothelial Cells Avoiding Macrophage Filtering. ACS Nano 2021, 15 (6) , 9701-9716. https://doi.org/10.1021/acsnano.1c00316
  16. Kellie D. Nance, Jordan L. Meier. Modifications in an Emergency: The Role of N1-Methylpseudouridine in COVID-19 Vaccines. ACS Central Science 2021, 7 (5) , 748-756. https://doi.org/10.1021/acscentsci.1c00197
  17. André E. Nel, Jeff F. Miller. Nano-Enabled COVID-19 Vaccines: Meeting the Challenges of Durable Antibody Plus Cellular Immunity and Immune Escape. ACS Nano 2021, 15 (4) , 5793-5818. https://doi.org/10.1021/acsnano.1c01845
  18. Monique C. P. Mendonça, Ayse Kont, Maria Rodriguez Aburto, John F. Cryan, Caitriona M. O’Driscoll. Advances in the Design of (Nano)Formulations for Delivery of Antisense Oligonucleotides and Small Interfering RNA: Focus on the Central Nervous System. Molecular Pharmaceutics 2021, 18 (4) , 1491-1506. https://doi.org/10.1021/acs.molpharmaceut.0c01238
  19. Keshava L. Jetha, Praful D. Bharadia, Manish P. Patel. Nanotechnology and Vaccine Development. 2024, 63-93. https://doi.org/10.1002/9781394175482.ch3
  20. Yosra Saad, Mohamed Bouzid, Marwa Selmi, Mohamed Hichem Gazzah, Ahmed Mansour Almansour, Amira Yahia Boshra, Sofiene Mohamed Habib Mansouri, Hafedh Belmabrouk. The adsorption effect on chemical kinetics at the reaction surface in a microfluidic channel of a biosensor for the SARS-Cov-2 detection. Sensors and Actuators A: Physical 2024, 369 , 115175. https://doi.org/10.1016/j.sna.2024.115175
  21. Rasha E. Gheith, Eman Elsebaie, Abeer Kandeel, Shaimaa Badran. The impact of corona virus disease-2019 (COVID-19) vaccination on patients with systemic rheumatic diseases attending a tertiary care university-based hospital. The Egyptian Rheumatologist 2024, 46 (2) , 73-77. https://doi.org/10.1016/j.ejr.2024.01.004
  22. Umair Ilyas, Sarmad Sheraz Jadoon, Tanzeel Ahmed, Reem Altaf, Aslam Khan, Ashfaq Ahmad, Yasir Rasool, Syed Muzzammil Masaud, Zakir Khan. COVID-19 and progress in therapeutic approaches: a narrative review. Cukurova Medical Journal 2024, 49 (1) , 204-223. https://doi.org/10.17826/cumj.1394329
  23. Rui Gao, Xinxin Xu, Prashant Kumar, Ye Liu, Hongyu Zhang, Xiao Guo, Maozhong Sun, Felippe Mariano Colombari, André F. de Moura, Changlong Hao, Jessica Ma, Emine Sumeyra Turali Emre, Minjeong Cha, Liguang Xu, Hua Kuang, Nicholas A. Kotov, Chuanlai Xu. Tapered chiral nanoparticles as broad-spectrum thermally stable antivirals for SARS-CoV-2 variants. Proceedings of the National Academy of Sciences 2024, 121 (13) https://doi.org/10.1073/pnas.2310469121
  24. June Park. Expertise as a Response to Limited Multilateralism: The Case of South Korea's Vaccine Procurement Task Force for COVID-19 Vaccines amid Unequal Access via the COVAX Facility. Journal of Health Politics, Policy and Law 2024, 49 (1) , 99-132. https://doi.org/10.1215/03616878-10910224
  25. Zichao Huang, Xinyu Zhuang, Liping Liu, Jiayu Zhao, Sheng Ma, Xinghui Si, Zhenyi Zhu, Fan Wu, Ningyi Jin, Mingyao Tian, Wantong Song, Xuesi Chen. Modularized viromimetic polymer nanoparticle vaccines (VPNVaxs) to elicit durable and effective humoral immune responses. National Science Review 2024, 11 (3) https://doi.org/10.1093/nsr/nwad310
  26. Vivek P. Chavda, Eswara Naga Hanuma Kumar Ghali, Pankti C. Balar, Subhash C. Chauhan, Nikita Tiwari, Somanshi Shukla, Mansi Athalye, Vandana Patravale, Vasso Apostolopoulos, Murali M. Yallapu. Protein subunit vaccines: Promising frontiers against COVID-19. Journal of Controlled Release 2024, 366 , 761-782. https://doi.org/10.1016/j.jconrel.2024.01.017
  27. Elizabeth Ogando-Rivas, Paul Castillo, Changlin Yang, Vrunda Trivedi, Dingpeng Zhang, Fernanda Pohl-Guimarães, Ruixuan Liu, Arnav Barpujari, Kate M. Candelario, Hector Mendez-Gomez, Elias J. Sayour, Duane A. Mitchell. Expanded specific T cells to hypomutated regions of the SARS-CoV-2 using mRNA electroporated antigen presenting cells.. Molecular Therapy - Methods & Clinical Development 2024, , 101192. https://doi.org/10.1016/j.omtm.2024.101192
  28. Eleni Lampropoulou, Claus Benz, George J. Kahaly, Dagmar Führer. Thyroid Inflammation and Immunity During the COVID-19 Pandemic: A Comprehensive Review and Case Study. Hormone and Metabolic Research 2023, https://doi.org/10.1055/a-2222-6300
  29. Petra Kiszel, Pál Sík, János Miklós, Erika Kajdácsi, György Sinkovits, László Cervenak, Zoltán Prohászka. Class switch towards spike protein-specific IgG4 antibodies after SARS-CoV-2 mRNA vaccination depends on prior infection history. Scientific Reports 2023, 13 (1) https://doi.org/10.1038/s41598-023-40103-x
  30. Beata M. Szydłowska, Zizhen Cai, Mark C. Hersam. Printed nanomaterial sensor platforms for COVID-19 and future pandemics. Current Opinion in Solid State and Materials Science 2023, 27 (6) , 101121. https://doi.org/10.1016/j.cossms.2023.101121
  31. Xueqing Wang, Lulu Shi, Yirong Wang, Jia Chen, Zelan Yang, Chenglong Liu, Xiaomei Liu, Yang Li, Can Zhang, Anhui Sun, Huan Yan, Hui Sun. Effects of the glycosylation of the receptor binding domain (RBD dimer)-based Covid-19 vaccine (ZF2001) on its humoral immunogenicity and immunoreactivity. International Journal of Biological Macromolecules 2023, 253 , 126874. https://doi.org/10.1016/j.ijbiomac.2023.126874
  32. Muhammad Ovais, Guofang Zhang, Yang Li. Tailoring multivalent nanomedicines for monkeypox. Nano Today 2023, 52 , 101971. https://doi.org/10.1016/j.nantod.2023.101971
  33. Dima A. Sabbah, Rima Hajjo, Suhair Sunoqrot. A Critical Assessment of COVID-19 Genomic Vaccines. Current Topics in Medicinal Chemistry 2023, 23 (27) , 2552-2589. https://doi.org/10.2174/1568026623666230825094341
  34. Katerina Xekouki, Nefeli Lagopati, Costas Demetzos, Maria Gazouli, Natassa Pippa. A mini review for lipid-based nanovaccines: from their design to their applications. Journal of Liposome Research 2023, 33 (3) , 214-233. https://doi.org/10.1080/08982104.2023.2170408
  35. Rabeya Tajnur, Refaya Rezwan, Md. Abdul Aziz, Mohammad Safiqul Islam. An update on vaccine status and the role of nanomedicine against SARS‐CoV‐2: A narrative review. Health Science Reports 2023, 6 (7) https://doi.org/10.1002/hsr2.1377
  36. Hao Wu, Long Zhang, Hong-Li Li, Zhidong Teng. Stability analysis and optimal control on a multi-strain coinfection model with amplification and vaccination. Results in Physics 2023, 50 , 106556. https://doi.org/10.1016/j.rinp.2023.106556
  37. Tiana Loan Young, Kevin Chang Wang, Andrew James Varley, Bowen Li. Clinical delivery of circular RNA: Lessons learned from RNA drug development. Advanced Drug Delivery Reviews 2023, 197 , 114826. https://doi.org/10.1016/j.addr.2023.114826
  38. Guillermo Moreno‐Alcántar, Pierre Picchetti, Angela Casini. Gold Complexes in Anticancer Therapy: From New Design Principles to Particle‐Based Delivery Systems. Angewandte Chemie 2023, 135 (22) https://doi.org/10.1002/ange.202218000
  39. Guillermo Moreno‐Alcántar, Pierre Picchetti, Angela Casini. Gold Complexes in Anticancer Therapy: From New Design Principles to Particle‐Based Delivery Systems. Angewandte Chemie International Edition 2023, 62 (22) https://doi.org/10.1002/anie.202218000
  40. Jessica Fernanda Affonso de Oliveira, Zhongchao Zhao, Yi Xiang, Matthew D. Shin, Kathleen Elizabeth Villaseñor, Xinyi Deng, Sourabh Shukla, Shaochen Chen, Nicole F. Steinmetz. COVID-19 vaccines based on viral nanoparticles displaying a conserved B-cell epitope show potent immunogenicity and a long-lasting antibody response. Frontiers in Microbiology 2023, 14 https://doi.org/10.3389/fmicb.2023.1117494
  41. Daniela Liggett, Andrea Herbert, Renuka Badhe, Gina E.C. Charnley, K.P.C. Hudson, Ilan Kelman, Won Sang Lee, Cristian Lorenzo, Pedro Marques-Quinteiro, Meredith Nash, Jennifer Pickett, Yelena Yermakova. Researchers on ice? How the COVID-19 pandemic has impacted Antarctic researchers. Antarctic Science 2023, 35 (2) , 141-160. https://doi.org/10.1017/S0954102023000020
  42. Galal Mohsen Hussein Al-Sayadi, Abhishek Verma, Yash Choudhary, Pallavi Sandal, Preeti Patel, Dilpreet Singh, Ghanshyam Das Gupta, Balak Das Kurmi. Solid Lipid Nanoparticles (SLNs): Advancements in Modification Strategies Toward Drug Delivery Vehicle. Pharmaceutical Nanotechnology 2023, 11 (2) , 138-154. https://doi.org/10.2174/2211738511666221026163303
  43. Marco Hoffmann, Sven Gerlach, Masanari Takamiya, Samar Tarazi, Nils Hersch, Agnes Csiszár, Ronald Springer, Georg Dreissen, Hanno Scharr, Sepand Rastegar, Tanja Beil, Uwe Strähle, Rudolf Merkel, Bernd Hoffmann. Smuggling on the Nanoscale—Fusogenic Liposomes Enable Efficient RNA-Transfer with Negligible Immune Response In Vitro and In Vivo. Pharmaceutics 2023, 15 (4) , 1210. https://doi.org/10.3390/pharmaceutics15041210
  44. Girolamo Giannotta, Antonio Murrone, Nicola Giannotta. COVID-19 mRNA Vaccines: The Molecular Basis of Some Adverse Events. Vaccines 2023, 11 (4) , 747. https://doi.org/10.3390/vaccines11040747
  45. Li Wong, Haridah Alias, Yee Wong, Megat Megat Hashim, Yulan Lin, Zhijian Hu. COVID-19 Anti-Vaccine Sentiments in Malaysia: Narratives of Comments from Facebook Post. Vaccines 2023, 11 (4) , 834. https://doi.org/10.3390/vaccines11040834
  46. Anete Ogrina, Ina Balke, Ieva Kalnciema, Dace Skrastina, Juris Jansons, Martin F. Bachmann, Andris Zeltins. Bacterial expression systems based on Tymovirus-like particles for the presentation of vaccine antigens. Frontiers in Microbiology 2023, 14 https://doi.org/10.3389/fmicb.2023.1154990
  47. Yijiao Qu, Robert De Rose, Chan‐Jin Kim, Jiajing Zhou, Zhixing Lin, Yi Ju, Sukhvir Kaur Bhangu, Christina Cortez‐Jugo, Francesca Cavalieri, Frank Caruso. Supramolecular Polyphenol‐DNA Microparticles for In Vivo Adjuvant and Antigen Co‐Delivery and Immune Stimulation. Angewandte Chemie International Edition 2023, 62 (12) https://doi.org/10.1002/anie.202214935
  48. Yijiao Qu, Robert De Rose, Chan‐Jin Kim, Jiajing Zhou, Zhixing Lin, Yi Ju, Sukhvir Kaur Bhangu, Christina Cortez‐Jugo, Francesca Cavalieri, Frank Caruso. Supramolecular Polyphenol‐DNA Microparticles for In Vivo Adjuvant and Antigen Co‐Delivery and Immune Stimulation. Angewandte Chemie 2023, 135 (12) https://doi.org/10.1002/ange.202214935
  49. Yvonne Hojberg, Mahmuod Abdeljaber, Joseph A. Prahlow. Generalized Eosinophilia Following Moderna COVID-19 Vaccine Administration: A Case Report. Academic Forensic Pathology 2023, 13 (1) , 9-15. https://doi.org/10.1177/19253621231157933
  50. Ajay Manaithiya, Ozair Alam, Shruti Mittal, Mohd. Javed Naim, Mohd. Imran, Ahmed Subeh Alshrari, Aadil A. Sheikh, Imran A. Khan. An Updated and Focused Review on Heterocyclic Inhibitors for SARSCoV and SARS-CoV-2 3CLpro. Mini-Reviews in Medicinal Chemistry 2023, 23 (5) , 576-632. https://doi.org/10.2174/1389557522666220511125102
  51. Vivek P. Chavda, Gargi Jogi, Srusti Dave, Bhoomika M. Patel, Lakshmi Vineela Nalla, Krishna Koradia. mRNA-Based Vaccine for COVID-19: They Are New but Not Unknown!. Vaccines 2023, 11 (3) , 507. https://doi.org/10.3390/vaccines11030507
  52. Phuoc Loc Truong, Yiming Yin, Daeho Lee, Seung Hwan Ko. Advancement in COVID‐19 detection using nanomaterial‐based biosensors. Exploration 2023, 3 (1) https://doi.org/10.1002/EXP.20210232
  53. Alaa A.A. Aljabali, Rasha M. Bashatwah, Mohammad A. Obeid, Vijay Mishra, Yachana Mishra, Ángel Serrano-Aroca, Kenneth Lundstrom, Murtaza M. Tambuwala. Current state of, prospects for, and obstacles to mRNA vaccine development. Drug Discovery Today 2023, 28 (2) , 103458. https://doi.org/10.1016/j.drudis.2022.103458
  54. Francesca Gorini, Cristina Vassalle. A Literature Review on SARS-CoV-2 and Other Viruses in Thyroid Disorders: Environmental Triggers or No-Guilty Bystanders?. International Journal of Environmental Research and Public Health 2023, 20 (3) , 2389. https://doi.org/10.3390/ijerph20032389
  55. Qi Wei, Shixian Liu, Xu Huang, Hua Xin, Jianxun Ding. Immunologically effective biomaterials-enhanced vaccines against infection of pathogenic microorganisms. Biosafety and Health 2023, 5 (1) , 45-61. https://doi.org/10.1016/j.bsheal.2022.11.002
  56. Shibli Nisar, Abdul Wakeel, Wania Tahir, Muhammad Tariq. Minimizing Viral Transmission in COVID-19 Like Pandemics: Technologies, Challenges, and Opportunities. IEEE Sensors Journal 2023, 23 (2) , 922-932. https://doi.org/10.1109/JSEN.2022.3170521
  57. Anurag Singh, Simran P. Kaur, Mohd Fardeen Husain Shahanshah, Bhawna Sharma, Vijay K. Chaudhary, Sanjay Gupta, Vandana Gupta. COVID‐19 Vaccination. 2023, 472-493. https://doi.org/10.1002/9781119789741.ch22
  58. Sayoni Ray, Armando Puente, Nicole F. Steinmetz, Jonathan K. Pokorski. Recent advancements in single dose slow‐release devices for prophylactic vaccines. WIREs Nanomedicine and Nanobiotechnology 2023, 15 (1) https://doi.org/10.1002/wnan.1832
  59. Priya Shrivastava, Suresh P. Vyas. COVID-19: Molecular Pathogenesis and Prospective Therapeutic Interventions. 2023, 269-294. https://doi.org/10.1007/978-3-031-20537-8_12
  60. Árpád Ferenc Kovács. Gene Therapy of Extracellular Vesicles in Cardiovascular and Metabolic Diseases. 2023, 207-228. https://doi.org/10.1007/978-981-99-1443-2_14
  61. Tetsuya Akaishi, Tamotsu Onodera, Tatsuya Takahashi, Hideo Harigae, Tadashi Ishii. Acute Adverse Events at a Mass Vaccination Site after the Third and Fourth COVID-19 Vaccinations in Japan. The Tohoku Journal of Experimental Medicine 2023, 259 (4) , 263-271. https://doi.org/10.1620/tjem.2023.J002
  62. Donghwan Jeon, Douglas G. McNeel. Toll-like receptor agonist combinations augment mouse T-cell anti-tumor immunity via IL-12- and interferon ß-mediated suppression of immune checkpoint receptor expression. OncoImmunology 2022, 11 (1) https://doi.org/10.1080/2162402X.2022.2054758
  63. Marco Hoffmann, Sven Gerlach, Christina Hoffmann, Nathalie Richter, Nils Hersch, Agnes Csiszár, Rudolf Merkel, Bernd Hoffmann. PEGylation and folic-acid functionalization of cationic lipoplexes—Improved nucleic acid transfer into cancer cells. Frontiers in Bioengineering and Biotechnology 2022, 10 https://doi.org/10.3389/fbioe.2022.1066887
  64. Chavee Laomeephol, Sudartip Areecheewakul, Supannikar Tawinwung, Koramit Suppipat, Preedakorn Chunhacha, Nuno M. Neves, Jittima Amie Luckanagul. Potential roles of hyaluronic acid in in vivo CAR T cell reprogramming for cancer immunotherapy. Nanoscale 2022, 14 (48) , 17821-17840. https://doi.org/10.1039/D2NR05949E
  65. Mesfin Tafa Segni, Hailu Fekadu Demissie, Muhammedawel Kaso Adem, Adem Kedir Geleto, Mesfin Wubishet Kelkile, Birhanu Kenate Sori, Melese Lemmi Heyi, Dhabesa Gobena Iticha, Gemechu Shumi Bejiga, Abera Botere Guddisa, Yadeta Ayana Sima, Lemessa Tadesse Amente, Dereje Abdena Bayisa, Mengistu Bekele Hurisa, Tesfaye Kebebew Jiru, . Post COVID-19 vaccination side effects and associated factors among vaccinated health care providers in Oromia region, Ethiopia in 2021. PLOS ONE 2022, 17 (12) , e0278334. https://doi.org/10.1371/journal.pone.0278334
  66. R. M. Ruggeri, L. Giovanellla, A. Campennì. SARS-CoV-2 vaccine may trigger thyroid autoimmunity: real-life experience and review of the literature. Journal of Endocrinological Investigation 2022, 45 (12) , 2283-2289. https://doi.org/10.1007/s40618-022-01863-x
  67. Mostafa Yosef, Fatma Amr Gamil Mokhtar, Wafaa Mohamed Hussein. Compliance with wearing facemasks by university teaching staff during the second wave of COVID-19 pandemic: a cross sectional study. Discover Social Science and Health 2022, 2 (1) https://doi.org/10.1007/s44155-022-00011-3
  68. Hezhi Wang, Lu Qin, Xin Zhang, Jian Guan, Shirui Mao. Mechanisms and challenges of nanocarriers as non-viral vectors of therapeutic genes for enhanced pulmonary delivery. Journal of Controlled Release 2022, 352 , 970-993. https://doi.org/10.1016/j.jconrel.2022.10.061
  69. Ye Cao, Yang Fei Tan, Yee Shan Wong, Muhammad Aminuddin, Bhuthalingam Ramya, Melvin Wen Jie Liew, Jiaxin Liu, Subbu S. Venkatraman. Designing siRNA/chitosan-methacrylate complex nanolipogel for prolonged gene silencing effects. Scientific Reports 2022, 12 (1) https://doi.org/10.1038/s41598-022-07554-0
  70. Lifeng Wang, Zhiwei Li. Smart Nanostructured Materials for SARS-CoV-2 and Variants Prevention, Biosensing and Vaccination. Biosensors 2022, 12 (12) , 1129. https://doi.org/10.3390/bios12121129
  71. Hannah Krivić, Sebastian Himbert, Maikel C. Rheinstädter. Perspective on the Application of Erythrocyte Liposome-Based Drug Delivery for Infectious Diseases. Membranes 2022, 12 (12) , 1226. https://doi.org/10.3390/membranes12121226
  72. Lingyao Kong, Xiaofei Wang, Hongxi Chen, Ziyan Shi, Yanlin Lang, Ying Zhang, Hongyu Zhou. Relapses after SARS-CoV-2 vaccination in patients with neuromyelitis optica spectrum disorder and multiple sclerosis. Multiple Sclerosis and Related Disorders 2022, 68 , 104167. https://doi.org/10.1016/j.msard.2022.104167
  73. Agustín Valenzuela-Fernández, Romina Cabrera-Rodriguez, Laura Ciuffreda, Silvia Perez-Yanes, Judith Estevez-Herrera, Rafaela González-Montelongo, Julia Alcoba-Florez, Rodrigo Trujillo-González, Diego García-Martínez de Artola, Helena Gil-Campesino, Oscar Díez-Gil, José M. Lorenzo-Salazar, Carlos Flores, Jonay Garcia-Luis. Nanomaterials to combat SARS-CoV-2: Strategies to prevent, diagnose and treat COVID-19. Frontiers in Bioengineering and Biotechnology 2022, 10 https://doi.org/10.3389/fbioe.2022.1052436
  74. Xiaojun Gao, Dan Fang, Yu Liang, Xin Deng, Ni Chen, Min Zeng, Mao Luo. Circular RNAs as emerging regulators in COVID-19 pathogenesis and progression. Frontiers in Immunology 2022, 13 https://doi.org/10.3389/fimmu.2022.980231
  75. Guillermo Aquino-Jarquin. The patent dispute over the breakthrough mRNA technology. Frontiers in Bioengineering and Biotechnology 2022, 10 https://doi.org/10.3389/fbioe.2022.1049873
  76. Kevork Oliver Messerian, Anton Zverev, Jack F. Kramarczyk, Andrew L. Zydney. Pressure‐dependent fouling behavior during sterile filtration of mRNA‐containing lipid nanoparticles. Biotechnology and Bioengineering 2022, 119 (11) , 3221-3229. https://doi.org/10.1002/bit.28200
  77. Virginia Recchia, Alessandra Aloisi, Antonella Zizza. Risk management and communication plans from SARS to COVID‐19 and beyond. The International Journal of Health Planning and Management 2022, 37 (6) , 3039-3060. https://doi.org/10.1002/hpm.3545
  78. Cristina de la Torre, Pablo Játiva, Inmaculada Posadas, Darío Manzanares, José L. Jiménez Blanco, Carmen Ortiz Mellet, José Manuel García Fernández, Valentín Ceña. A β-Cyclodextrin-Based Nanoparticle with Very High Transfection Efficiency Unveils siRNA-Activated TLR3 Responses in Human Prostate Cancer Cells. Pharmaceutics 2022, 14 (11) , 2424. https://doi.org/10.3390/pharmaceutics14112424
  79. Federica Sommonte, Edward Weaver, Essyrose Mathew, Nunzio Denora, Dimitrios A. Lamprou. In-House Innovative “Diamond Shaped” 3D Printed Microfluidic Devices for Lysozyme-Loaded Liposomes. Pharmaceutics 2022, 14 (11) , 2484. https://doi.org/10.3390/pharmaceutics14112484
  80. Yiran E. Li, Shuyi Wang, Russel J. Reiter, Jun Ren. Clinical cardiovascular emergencies and the cellular basis of COVID-19 vaccination: from dream to reality?. International Journal of Infectious Diseases 2022, 124 , 1-10. https://doi.org/10.1016/j.ijid.2022.08.026
  81. Esther Jacobs, Kaije Qian, Valerie L. Pietsch, Margarethe Richter, David S. Jones, Gavin P. Andrews, Yiwei Tian. Design and scale-up of amorphous drug nanoparticles production via a one-step anhydrous continuous process. International Journal of Pharmaceutics 2022, 628 , 122304. https://doi.org/10.1016/j.ijpharm.2022.122304
  82. Abdul Khaliq Mokhtar, Norsyahidah Mohd Hidzir, Faizal Mohamed, Irman Abdul Rahman, Syazwani Mohd Fadzil, Afifah Mardhiah Mohamed Radzi, Nur Ain Mohd Radzali. Gold nanoparticles as radiosensitizer for radiotherapy and diagnosis of COVID-19: A review. Nanoscale and Microscale Thermophysical Engineering 2022, 26 (4) , 161-187. https://doi.org/10.1080/15567265.2022.2138803
  83. Ziqi Wang, Kai Cui, Ulrich Costabel, Xiaoju Zhang. Nanotechnology‐facilitated vaccine development during the coronavirus disease 2019 (COVID‐19) pandemic. Exploration 2022, 2 (5) https://doi.org/10.1002/EXP.20210082
  84. Berna İmge Aydoğan, Uğur Ünlütürk, Mustafa Cesur. Type 1 diabetes mellitus following SARS-CoV-2 mRNA vaccination. Endocrine 2022, 78 (1) , 42-46. https://doi.org/10.1007/s12020-022-03130-8
  85. Haoyang Tong, Chaoyu Cao, Minli You, Shuang Han, Zhe Liu, Ying Xiao, Wanghong He, Chang Liu, Ping Peng, Zhenrui Xue, Yan Gong, Chunyan Yao, Feng Xu. Artificial intelligence-assisted colorimetric lateral flow immunoassay for sensitive and quantitative detection of COVID-19 neutralizing antibody. Biosensors and Bioelectronics 2022, 213 , 114449. https://doi.org/10.1016/j.bios.2022.114449
  86. Amgad Muneer, Suliman Mohamed Fati, Nur Arifin Akbar, David Agustriawan, Setyanto Tri Wahyudi. iVaccine-Deep: Prediction of COVID-19 mRNA vaccine degradation using deep learning. Journal of King Saud University - Computer and Information Sciences 2022, 34 (9) , 7419-7432. https://doi.org/10.1016/j.jksuci.2021.10.001
  87. Diksha Nagpal, Shakti Nagpal, Deepak Kaushik, Himanshu Kathuria. Current clinical status of new COVID-19 vaccines and immunotherapy. Environmental Science and Pollution Research 2022, 384 https://doi.org/10.1007/s11356-022-22661-1
  88. Madeline J. Hooper, Francesca L. Veon, Tessa M. LeWitt, Christopher Chung, Jaehyuk Choi, Xiaolong A. Zhou, Joan Guitart. Cutaneous T-Cell–Rich Lymphoid Infiltrates After SARS-CoV-2 Vaccination. JAMA Dermatology 2022, 158 (9) , 1073. https://doi.org/10.1001/jamadermatol.2022.2383
  89. Yixin Wang, Ting‐Jing Chen‐Mayfield, Zhaoting Li, Muhsin H. Younis, Weibo Cai, Quanyin Hu. Harnessing DNA for Immunotherapy: Cancer, Infectious Diseases, and Beyond. Advanced Functional Materials 2022, 32 (37) https://doi.org/10.1002/adfm.202112273
  90. Farhad Nosrati Nejad, Mohammad Ali Mohammadi Gharehghani, Sina Ahmadi. Collective and individual rationality dilemma and the failure of anti-Covid-19 policies: Why some people don't wear masks?. International Journal of Surgery 2022, 105 , 106866. https://doi.org/10.1016/j.ijsu.2022.106866
  91. Mahtab Moshref Javadi, Mozhgan Taghdisi Hosseinzadeh, Neda Soleimani, Foad Rommasi. Evaluating the immunogenicity of gold nanoparticles conjugated RBD with Freund's adjuvant as a potential vaccine against SARS-CoV-2. Microbial Pathogenesis 2022, 170 , 105687. https://doi.org/10.1016/j.micpath.2022.105687
  92. Panchanan Sahoo, Jyotirmayee Dey, Soumya Ranjan Mahapatra, Arpan Ghosh, Aryan Jaiswal, Santwana Padhi, Samudyata C. Prabhuswamimath, Namrata Misra, Mrutyunjay Suar. Nanotechnology and COVID-19 Convergence: Toward New Planetary Health Interventions Against the Pandemic. OMICS: A Journal of Integrative Biology 2022, 26 (9) , 473-488. https://doi.org/10.1089/omi.2022.0072
  93. Evelien Hesemans, Kiana Buttiens, Bella Manshian, Stefaan Soenen. The Role of Optical Imaging in Translational Nanomedicine. Journal of Functional Biomaterials 2022, 13 (3) , 137. https://doi.org/10.3390/jfb13030137
  94. Halina Mikolajek, Miriam Weckener, Z. Faidon Brotzakis, Jiandong Huo, Evmorfia V. Dalietou, Audrey Le Bas, Pietro Sormanni, Peter J. Harrison, Philip N. Ward, Steven Truong, Lucile Moynie, Daniel K. Clare, Maud Dumoux, Joshua Dormon, Chelsea Norman, Naveed Hussain, Vinod Vogirala, Raymond J. Owens, Michele Vendruscolo, James H. Naismith. Correlation between the binding affinity and the conformational entropy of nanobody SARS-CoV-2 spike protein complexes. Proceedings of the National Academy of Sciences 2022, 119 (31) https://doi.org/10.1073/pnas.2205412119
  95. Rui Gao, Liguang Xu, Maozhong Sun, Manlin Xu, Changlong Hao, Xiao Guo, Felippe Mariano Colombari, Xin Zheng, Petr Král, André F. de Moura, Chuanlai Xu, Jinguang Yang, Nicholas A. Kotov, Hua Kuang. Site-selective proteolytic cleavage of plant viruses by photoactive chiral nanoparticles. Nature Catalysis 2022, 5 (8) , 694-707. https://doi.org/10.1038/s41929-022-00823-1
  96. Juny Sebastian, Merrin Mathew, Veeranna Sharsty, Madhan Ramesh. Leukocytoclastic Vasculitis Following COVID-19 Vaccination: A Case Report. Hospital Pharmacy 2022, 57 (4) , 564-567. https://doi.org/10.1177/00185787211067379
  97. Amal Hasan, Hossein Arefanian, Arshad Mohamed Channanath, Irina AlKhairi, Preethi Cherian, Sriraman Devarajan, Thangavel Alphonse Thanaraj, Mohamed Abu-Farha, Jehad Abubaker, Fahd Al-Mulla. Association of COVID-19 Vaccines ChAdOx1-S and BNT162b2 with Circulating Levels of Coagulation Factors and Antithrombin. Vaccines 2022, 10 (8) , 1226. https://doi.org/10.3390/vaccines10081226
  98. Rand Dawoud, Daniel Haddad, Viraj Shah, Vraj Patel, Gohar Abbas, Sai Guduru, Amulya Dakka, Vishrut Kaushik, Pramil Cheriyath. COVID-19 Vaccine-Related Arthritis: A Descriptive Study of Case Reports on a Rare Complication. Cureus 2022, 12 https://doi.org/10.7759/cureus.26702
  99. Anaïs M. Quemener, Marie‐Dominique Galibert. Antisense oligonucleotide: A promising therapeutic option to beat COVID ‐19. WIREs RNA 2022, 13 (4) https://doi.org/10.1002/wrna.1703
  100. Tore Skotland, Tore Geir Iversen, Alicia Llorente, Kirsten Sandvig. Biodistribution, pharmacokinetics and excretion studies of intravenously injected nanoparticles and extracellular vesicles: Possibilities and challenges. Advanced Drug Delivery Reviews 2022, 186 , 114326. https://doi.org/10.1016/j.addr.2022.114326
Load more citations
Download PDF

  • Abstract

    High Resolution Image
    Download MS PowerPoint Slide

    Figure 1

    Figure 1. Vaccine types currently under development for SARS-CoV-2. (a) Inactivated vaccine that uses the native virus rendered replication deficient from heat or chemical treatment, (b) live-attenuated vaccine that can replicate, but in a limited manner that cannot cause the disease, (c) subunit vaccine that incorporates subsections of the native virus such as the S protein, (d) viral vector vaccine that encapsulates the genome of a different weakly pathogenic virus with additional DNA that encodes the target viral antigen, (e) DNA vaccine using a DNA plasmid that encodes the target antigen, often administered by electroporation, (f) RNA vaccine of RNA encapsulated within a LNP to decrease RNA degradation and increase translation efficiency. Graphics created with Biorender.com.

    High Resolution Image
    Download MS PowerPoint Slide

    Figure 2

    Figure 2. Graphs detailing the vaccines currently in development for SARS-CoV-2 according to the WHO and the Milken Institute as of August 11, 2020. (a) Pie chart of the vaccines by type, (b) bar graph showing the number of vaccines using adjuvants, (c) bar graph of the vaccine candidates in clinical trials.

    High Resolution Image
    Download MS PowerPoint Slide

  • References

    ARTICLE SECTIONS
    Jump To

    This article references 157 other publications.

    1. 1
      Cascella, M.; Rajnik, M.; Cuomo, A.; Dulebohn, S. C.; Di Napoli, R. Features, Evaluation and Treatment Coronavirus (COVID-19). In StatPearls; StatPearls Publishing: Treasure Island (FL), 2020.
      There is no corresponding record for this reference.
    2. 2
      Astuti, I. Ysrafil. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): An Overview of Viral Structure and Host Response. Diabetes Metab Syndr 2020, 14, 407– 412,  DOI: 10.1016/j.dsx.2020.04.020
      2
      Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): An overview of viral structure and host response
      Astuti Indwiani; Ysrafil
      Diabetes & metabolic syndrome (2020), 14 (4), 407-412 ISSN:.
      BACKGROUND AND AIM: As a result of its rapid spread in various countries around the world, on March 11, 2020, WHO issued an announcement of the change in coronavirus disease 2019 status from epidemic to pandemic disease. The virus that causes this disease is indicated originating from animals traded in a live animal market in Wuhan, China. Severe Acute Respiratory Syndrome Coronavirus 2 can attack lung cells because there are many conserved receptor entries, namely Angiotensin Converting Enzyme-2. The presence of this virus in host cells will initiate various protective responses leading to pneumonia and Acute Respiratory Distress Syndrome. This review aimed to provide an overview related to this virus and examine the body's responses and possible therapies. METHOD: We searched PubMed databases for Severe Acute Respiratory Syndrome Coronavirus-2, Middle East respiratory syndrome-related coronavirus and Severe Acute Respiratory Syndrome Coronavirus. Full texts were retrieved, analyzed and developed into an easy-to-understand review. RESULTS: We provide a complete review related to structure, origin, and how the body responds to this virus infection and explain the possibility of an immune system over-reaction or cytokine storm. We also include an explanation of how this virus creates modes of avoidance to evade immune system attacks. We further explain the therapeutic approaches that can be taken in the treatment and prevention of this viral infection. CONCLUSION: In summary, based on the structural and immune-evasion system of coronavirus, we suggest several approaches to treat the disease.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB38zps12nsw%253D%253D&md5=a417c9c08407e769309a5f530b719587
    3. 3
      WHO Coronavirus Disease (COVID-19) Dashboard https://covid19.who.int (accessed 2020-08-3).
      There is no corresponding record for this reference.
    4. 4
      Washington, D. of C. 1100 C. A. N. S. 1300B; Dc 20036. PolitiFact - Cuomo Accurately Says that Other Countries that Reopened Saw an Increase in Coronavirus Infections. https://www.politifact.com/factchecks/2020/apr/20/andrew-cuomo/cuomo-accurately-says-other-countries-reopened-saw/ (accessed 2020-08-03).
      There is no corresponding record for this reference.
    5. 5
      Kissler, S. M.; Tedijanto, C.; Goldstein, E.; Grad, Y. H.; Lipsitch, M. Projecting the Transmission Dynamics of SARS-CoV-2 through the Postpandemic Period. Science 2020, 368, 860– 868,  DOI: 10.1126/science.abb5793
      5
      Projecting the transmission dynamics of SARS-CoV-2 through the postpandemic period
      Kissler, Stephen M.; Tedijanto, Christine; Goldstein, Edward; Grad, Yonatan H.; Lipsitch, Marc
      Science (Washington, DC, United States) (2020), 368 (6493), 860-868CODEN: SCIEAS; ISSN:1095-9203. (American Association for the Advancement of Science)
      It is urgent to understand the future of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) transmission. We used ests. of seasonality, immunity, and cross-immunity for human coronavirus OC43 (HCoV-OC43) and HCoV-HKU1 using time-series data from the United States to inform a model of SARS-CoV-2 transmission. We projected that recurrent wintertime outbreaks of SARS-CoV-2 will probably occur after the initial, most severe pandemic wave. Absent other interventions, a key metric for the success of social distancing is whether crit. care capacities are exceeded. To avoid this, prolonged or intermittent social distancing may be necessary into 2022. Addnl. interventions, including expanded crit. care capacity and an effective therapeutic, would improve the success of intermittent distancing and hasten the acquisition of herd immunity. Longitudinal serol. studies are urgently needed to det. the extent and duration of immunity to SARS-CoV-2. Even in the event of apparent elimination, SARS-CoV-2 surveillance should be maintained because a resurgence in contagion could be possible as late as 2024.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhtVWnur%252FI&md5=3837e7a844f54a14bfc71f8dd1042b3a
    6. 6
      Wu, A.; Peng, Y.; Huang, B.; Ding, X.; Wang, X.; Niu, P.; Meng, J.; Zhu, Z.; Zhang, Z.; Wang, J.; Sheng, J.; Quan, L.; Xia, Z.; Tan, W.; Cheng, G.; Jiang, T. Genome Composition and Divergence of the Novel Coronavirus (2019-NCoV) Originating in China. Cell Host Microbe 2020, 27, 325– 328,  DOI: 10.1016/j.chom.2020.02.001
      6
      Genome Composition and Divergence of the Novel Coronavirus (2019-nCoV) Originating in China
      Wu, Aiping; Peng, Yousong; Huang, Baoying; Ding, Xiao; Wang, Xianyue; Niu, Peihua; Meng, Jing; Zhu, Zhaozhong; Zhang, Zheng; Wang, Jiangyuan; Sheng, Jie; Quan, Lijun; Xia, Zanxian; Tan, Wenjie; Cheng, Genhong; Jiang, Taijiao
      Cell Host & Microbe (2020), 27 (3), 325-328CODEN: CHMECB; ISSN:1931-3128. (Elsevier Inc.)
      An in-depth annotation of the newly discovered coronavirus (2019-nCoV) genome has revealed differences between 2019-nCoV and severe acute respiratory syndrome (SARS) or SARS-like coronaviruses. A systematic comparison identified 380 amino acid substitutions between these coronaviruses, which may have caused functional and pathogenic divergence of 2019-nCoV.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXivVeiu7s%253D&md5=3c036a5fdc31fae6e87fd2754c5018fc
    7. 7
      Draft Landscape of COVID-19 Candidate Vaccines. https://www.who.int/publications/m/item/draft-landscape-of-covid-19-candidate-vaccines (accessed 2020-08-03).
      There is no corresponding record for this reference.
    8. 8
      Moderna’s Work on a COVID-19 Vaccine Candidate, Moderna, Inc. https://www.modernatx.com/modernas-work-potential-vaccine-against-covid-19 (accessed 2020-08-03).
      There is no corresponding record for this reference.
    9. 9
      Chinese Clinical Trial Register (ChiCTR) - The World Health Organization International Clinical Trials Registered Organization Registered Platform. http://www.chictr.org.cn/showprojen.aspx?proj=52227 (accessed 2020-05-06).
      There is no corresponding record for this reference.
    10. 10
      Phase I, Open-Label, Dose-Ranging Study of the Safety and Immunogenicity of 2019-NCoV Vaccine (MRNA-1273) in Healthy Adults - Full Text View. ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT04283461 (accessed 2020-04-01).
      There is no corresponding record for this reference.
    11. 11
      Kim, Y. C.; Dema, B.; Reyes-Sandoval, A. COVID-19 Vaccines: Breaking Record Times to First-in-Human Trials. NPJ. Vaccines 2020,  DOI: 10.1038/s41541-020-0188-3
      There is no corresponding record for this reference.
    12. 12
      Singh, K.; Mehta, S. The Clinical Development Process for a Novel Preventive Vaccine: An Overview. J. Postgrad. Med. 2016, 62, 4– 11,  DOI: 10.4103/0022-3859.173187
      12
      The clinical development process for a novel preventive vaccine: An overview
      Singh K; Mehta S
      Journal of postgraduate medicine (2016), 62 (1), 4-11 ISSN:.
      Each novel vaccine candidate needs to be evaluated for safety, immunogenicity, and protective efficacy in humans before it is licensed for use. After initial safety evaluation in healthy adults, each vaccine candidate follows a unique development path. This article on clinical development gives an overview on the development path based on the expectations of various guidelines issued by the World Health Organization (WHO), the European Medicines Agency (EMA), and the United States Food and Drug Administration (USFDA). The manuscript describes the objectives, study populations, study designs, study site, and outcome(s) of each phase (Phase I-III) of a clinical trial. Examples from the clinical development of a malaria vaccine candidate, a rotavirus vaccine, and two vaccines approved for human papillomavirus (HPV) have also been discussed. The article also tabulates relevant guidelines, which can be referred to while drafting the development path of a novel vaccine candidate.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC28rnsVyjsQ%253D%253D&md5=49266943984be754033f61421d4ba6be
    13. 13
      Lee, W. S.; Wheatley, A. K.; Kent, S. J.; DeKosky, B. J. Antibody-Dependent Enhancement and SARS-CoV-2 Vaccines and Therapies. Nat. Microbiol. 2020, 5, 1185– 1191,  DOI: 10.1038/s41564-020-00789-5
      13
      Antibody-dependent enhancement and SARS-CoV-2 vaccines and therapies
      Lee, Wen Shi; Wheatley, Adam K.; Kent, Stephen J.; DeKosky, Brandon J.
      Nature Microbiology (2020), 5 (10), 1185-1191CODEN: NMAICH; ISSN:2058-5276. (Nature Research)
      A review. Antibody-based drugs and vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are being expedited through preclin. and clin. development. Data from the study of SARS-CoV and other respiratory viruses suggest that anti-SARS-CoV-2 antibodies could exacerbate COVID-19 through antibody-dependent enhancement (ADE). Previous respiratory syncytial virus and dengue virus vaccine studies revealed human clin. safety risks related to ADE, resulting in failed vaccine trials. Here, the authors describe key ADE mechanisms and discuss mitigation strategies for SARS-CoV-2 vaccines and therapies in development. The authors also outline recently published data to evaluate the risks and opportunities for antibody-based protection against SARS-CoV-2.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhvVyqurzJ&md5=d42e108c864dd793b68f21b459c304d0
    14. 14
      Schlake, T.; Thess, A.; Fotin-Mleczek, M.; Kallen, K.-J. Developing MRNA-Vaccine Technologies. RNA Biol. 2012, 9, 1319– 1330,  DOI: 10.4161/rna.22269
      14
      Developing mRNA-vaccine technologies
      Schlake, Thomas; Thess, Andreas; Fotin-Mleczek, Mariola; Kallen, Karl-Josef
      RNA Biology (2012), 9 (11), 1319-1330CODEN: RBNIBE; ISSN:1547-6286. (Landes Bioscience)
      A review. MRNA vaccines combine desirable immunol. properties with an outstanding safety profile and the unmet flexibility of genetic vaccines. Based on in situ protein expression, mRNA vaccines are capable of inducing a balanced immune response comprising both cellular and humoral immunity while not subject to MHC haplotype restriction. In addn., mRNA is an intrinsically safe vector as it is a minimal and only transient carrier of information that does not interact with the genome. Because any protein can be expressed from mRNA without the need to adjust the prodn. process, mRNA vaccines also offer max. flexibility with respect to development. Taken together, mRNA presents a promising vector that may well become the basis of a game-changing vaccine technol. platform. Here, we outline the current knowledge regarding different aspects that should be considered when developing an mRNA-based vaccine technol.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXjsFKktL8%253D&md5=5f3132e37cbf0b27ea1e128869d6dd11
    15. 15
      Dance, A. Coronavirus Vaccines Get a Biotech Boost. Nature 2020, 583, 647– 649,  DOI: 10.1038/d41586-020-02154-2
      15
      Coronavirus vaccines get a biotech boost
      Dance, Amber
      Nature (London, United Kingdom) (2020), 583 (7817), 647-649CODEN: NATUAS; ISSN:0028-0836. (Nature Research)
      Advances in technol. are accelerating the search for drugs to arm the immune system against SARS-CoV-2.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhsVahu7bE&md5=3bc5aa5ffd099cce41c163852b380651
    16. 16
      Thomas, K. U.S. Will Pay $1.6 Billion to Novavax for Coronavirus Vaccine. New York Times 2020, July 7.
      There is no corresponding record for this reference.
    17. 17
      Jackson, L. A.; Anderson, E. J.; Rouphael, N. G.; Roberts, P. C.; Makhene, M.; Coler, R. N.; McCullough, M. P.; Chappell, J. D.; Denison, M. R.; Stevens, L. J.; Pruijssers, A. J.; McDermott, A.; Flach, B.; Doria-Rose, N. A.; Corbett, K. S.; Morabito, K. M.; O’Dell, S.; Schmidt, S. D.; Swanson, P. A.; Padilla, M. An MRNA Vaccine against SARS-CoV-2 — Preliminary Report. N. Engl. J. Med. 2020, 0, null,  DOI: 10.1056/NEJMoa2022483
      There is no corresponding record for this reference.
    18. 18
      Novavax Announces Positive Phase 1 Data for Its COVID-19 Vaccine Candidate, Novavax Inc. IR Site. https://ir.novavax.com/news-releases/news-release-details/novavax-announces-positive-phase-1-data-its-covid-19-vaccine (accessed 2020-08-06).
      There is no corresponding record for this reference.
    19. 19
      Mulligan, M. J.; Lyke, K. E.; Kitchin, N.; Absalon, J.; Gurtman, A.; Lockhart, S. P.; Neuzil, K.; Raabe, V.; Bailey, R.; Swanson, K. A.; Li, P.; Koury, K.; Kalina, W.; Cooper, D.; Fonter-Garfias, C.; Shi, P.-Y.; Tuereci, O.; Tompkins, K. R.; Walsh, E. E.; Frenck, R., Phase 1/2 Study to Describe the Safety and Immunogenicity of a COVID-19 RNA Vaccine Candidate (BNT162b1) in Adults 18 to 55 Years of Age: Interim Report. medRxiv . 2020 2020.06.30.20142570.https://www.medrxiv.org/content/10.1101/2020.06.30.20142570v1.article-info (accessed 2020-08-06).
      There is no corresponding record for this reference.
    20. 20
      Sahin, U.; Muik, A.; Derhovanessian, E.; Vogler, I.; Kranz, L. M.; Vormehr, M.; Baum, A.; Pascal, K.; Quandt, J.; Maurus, D.; Brachtendorf, S.; Loerks, V. L.; Sikorski, J.; Hilker, R.; Becker, D.; Eller, A.-K.; Gruetzner, J.; Boesler, C.; Rosenbaum, C.; Kuehnle, M.-C., Concurrent Human Antibody and TH1 Type T-Cell Responses Elicited by a COVID-19 RNA Vaccine. medRxiv 2020, 2020.07.17.20140533. https://www.medrxiv.org/content/10.1101/2020.07.17.20140533v1.article-info (accessed 2020-08-06).
      There is no corresponding record for this reference.
    21. 21
      Zhu, F.-C.; Li, Y.-H.; Guan, X.-H.; Hou, L.-H.; Wang, W.-J.; Li, J.-X.; Wu, S.-P.; Wang, B.-S.; Wang, Z.; Wang, L.; Jia, S.-Y.; Jiang, H.-D.; Wang, L.; Jiang, T.; Hu, Y.; Gou, J.-B.; Xu, S.-B.; Xu, J.-J.; Wang, X.-W.; Wang, W. Safety, Tolerability, and Immunogenicity of a Recombinant Adenovirus Type-5 Vectored COVID-19 Vaccine: A Dose-Escalation, Open-Label, Non-Randomised, First-in-Human Trial. Lancet 2020, 395, 1845– 1854,  DOI: 10.1016/S0140-6736(20)31208-3
      21
      Safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 vectored COVID-19 vaccine: a dose-escalation, open-label, non-randomised, first-in-human trial
      Zhu, Feng-Cai; Li, Yu-Hua; Guan, Xu-Hua; Hou, Li-Hua; Wang, Wen-Juan; Li, Jing-Xin; Wu, Shi-Po; Wang, Bu-Sen; Wang, Zhao; Wang, Lei; Jia, Si-Yue; Jiang, Hu-Dachuan; Wang, Ling; Jiang, Tao; Hu, Yi; Gou, Jin-Bo; Xu, Sha-Bei; Xu, Jun-Jie; Wang, Xue-Wen; Wang, Wei; Chen, Wei
      Lancet (2020), 395 (10240), 1845-1854CODEN: LANCAO; ISSN:0140-6736. (Elsevier Ltd.)
      A vaccine to protect against COVID-19 is urgently needed. We aimed to assess the safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 (Ad5) vectored COVID-19 vaccine expressing the spike glycoprotein of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strain. We did a dose-escalation, single-center, open-label, non-randomized, phase 1 trial of an Ad5 vectored COVID-19 vaccine in Wuhan, China. Healthy adults 18-60 yr were sequentially enrolled and allocated to 1 of 3 dose groups (5 × 1010, 1 × 1011, and 1.5 × 1011 viral particles) to receive an i.m. injection of vaccine. The primary outcome was adverse events in the 7 days post-vaccination. Safety was assessed over 28 days post-vaccination. Specific antibodies were measured with ELISA, and the neutralizing antibody responses induced by vaccination were detected with SARS-CoV-2 virus neutralization and pseudovirus neutralization tests. T-cell responses were assessed by enzyme-linked immunospot and flow-cytometry assays. This study is registered with ClinicalTrials.gov, NCT04313127. Between March 16 and March 27, 2020, we screened 195 individuals for eligibility. Of them, 108 participants (51% male, 49% female; mean age 36.3 yr) were recruited and received the low dose (n=36), middle dose (n=36), or high dose (n=36) of the vaccine. All enrolled participants were included in the anal. At least 1 adverse reaction within the 1st 7 days after the vaccination was reported in 30 (83%) participants in the low dose group, 30 (83%) participants in the middle dose group, and 27 (75%) participants in the high dose group. The most common injection site adverse reaction was pain, which was reported in 58 (54%) vaccine recipients, and the most commonly reported systematic adverse reactions were fever (50 [46%]), fatigue (47 [44%]), headache (42 [39%]), and muscle pain (18 [17%]). Most adverse reactions that were reported in all dose groups were mild or moderate in severity. No serious adverse event was noted within 28 days post-vaccination. ELISA antibodies and neutralizing antibodies increased significantly at day 14, and peaked 28 days post-vaccination. Specific T-cell response peaked at day 14 post-vaccination. The Ad5 vectored COVID-19 vaccine is tolerable and immunogenic at 28 days post-vaccination. Humoral responses against SARS-CoV-2 peaked at day 28 post-vaccination in healthy adults, and rapid specific T-cell responses were noted from day 14 post-vaccination. Our findings suggest that the Ad5 vectored COVID-19 vaccine warrants further investigation.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhtVSjtrvO&md5=a14ff6459d359bd1743e3549191b3508
    22. 22
      Zhu, F.-C.; Guan, X.-H.; Li, Y.-H.; Huang, J.-Y.; Jiang, T.; Hou, L.-H.; Li, J.-X.; Yang, B.-F.; Wang, L.; Wang, W.-J.; Wu, S.-P.; Wang, Z.; Wu, X.-H.; Xu, J.-J.; Zhang, Z.; Jia, S.-Y.; Wang, B.-S.; Hu, Y.; Liu, J.-J.; Zhang, J. Immunogenicity and Safety of a Recombinant Adenovirus Type-5-Vectored COVID-19 Vaccine in Healthy Adults Aged 18 Years or Older: A Randomised, Double-Blind, Placebo-Controlled, Phase 2 Trial. Lancet 2020, 396, 479– 488,  DOI: 10.1016/S0140-6736(20)31605-6
      22
      Immunogenicity and safety of a recombinant adenovirus type-5-vectored COVID-19 vaccine in healthy adults aged 18 years or older: a randomised, double-blind, placebo-controlled, phase 2 trial
      Zhu, Feng-Cai; Guan, Xu-Hua; Li, Yu-Hua; Huang, Jian-Ying; Jiang, Tao; Hou, Li-Hua; Li, Jing-Xin; Yang, Bei-Fang; Wang, Ling; Wang, Wen-Juan; Wu, Shi-Po; Wang, Zhao; Wu, Xiao-Hong; Xu, Jun-Jie; Zhang, Zhe; Jia, Si-Yue; Wang, Bu-Sen; Hu, Yi; Liu, Jing-Jing; Zhang, Jun; Qian, Xiao-Ai; Li, Qiong; Pan, Hong-Xing; Jiang, Hu-Dachuan; Deng, Peng; Gou, Jin-Bo; Wang, Xue-Wen; Wang, Xing-Huan; Chen, Wei
      Lancet (2020), 396 (10249), 479-488CODEN: LANCAO; ISSN:0140-6736. (Elsevier Ltd.)
      This is the first randomised controlled trial for assessment of the immunogenicity and safety of a candidate non-replicating adenovirus type-5 (Ad5)-vectored COVID-19 vaccine, aiming to det. an appropriate dose of the candidate vaccine for an efficacy study. This randomised, double-blind, placebo-controlled, phase 2 trial of the Ad5-vectored COVID-19 vaccine was done in a single center in Wuhan, China. Healthy adults aged 18 years or older, who were HIV-neg. and previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-free, were eligible to participate and were randomly assigned to receive the vaccine at a dose of 1 x 1011 viral particles per mL or 5 x 1010 viral particles per mL, or placebo. Investigators allocated participants at a ratio of 2:1:1 to receive a single injection i.m. in the arm. The randomisation list (block size 4) was generated by an independent statistician. Participants, investigators, and staff undertaking lab. analyses were masked to group allocation. The primary endpoints for immunogenicity were the geometric mean titers (GMTs) of specific ELISA antibody responses to the receptor binding domain (RBD) and neutralising antibody responses at day 28. The primary endpoint for safety evaluation was the incidence of adverse reactions within 14 days. All recruited participants who received at least one dose were included in the primary and safety analyses. This study is registered with ClinicalTrials.gov, NCT04341389.603 volunteers were recruited and screened for eligibility between Apr. 11 and 16, 2020. 508 eligible participants (50% male; mean age 39·7 years, SD 12·5) consented to participate in the trial and were randomly assigned to receive the vaccine (1 x 1011 viral particles n=253; 5 x 1010 viral particles n=129) or placebo (n=126). In the 1 x 1011 and 5 x 1010 viral particles dose groups, the RBD-specific ELISA antibodies peaked at 656·5 (95% CI 575·2-749·2) and 571·0 (467·6-697·3), with seroconversion rates at 96% (95% CI 93-98) and 97% (92-99), resp., at day 28. Both doses of the vaccine induced significant neutralising antibody responses to live SARS-CoV-2, with GMTs of 19·5 (95% CI 16·8-22·7) and 18·3 (14·4-23·3) in participants receiving 1 x 1011 and 5 x 1010 viral particles, resp. Specific interferon γ enzyme-linked immunospot assay responses post vaccination were obsd. in 227 (90%, 95% CI 85-93) of 253 and 113 (88%, 81-92) of 129 participants in the 1 x 1011 and 5 x 1010 viral particles dose groups, resp. Solicited adverse reactions were reported by 183 (72%) of 253 and 96 (74%) of 129 participants in the 1 x 1011 and 5 x 1010 viral particles dose groups, resp. Severe adverse reactions were reported by 24 (9%) participants in the 1 x 1011 viral particles dose group and one (1%) participant in the 5 x 1010 viral particles dose group. No serious adverse reactions were documented. The Ad5-vectored COVID-19 vaccine at 5 x 1010 viral particles is safe, and induced significant immune responses in the majority of recipients after a single immunization. National Key R&D Program of China, National Science and Technol. Major Project, and CanSino Biologics.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhsVarsr7K&md5=29aae4e8cc67aa9c89c44be96c42f82d
    23. 23
      Folegatti, P. M.; Ewer, K. J.; Aley, P. K.; Angus, B.; Becker, S.; Belij-Rammerstorfer, S.; Bellamy, D.; Bibi, S.; Bittaye, M.; Clutterbuck, E. A.; Dold, C.; Faust, S. N.; Finn, A.; Flaxman, A. L.; Hallis, B.; Heath, P.; Jenkin, D.; Lazarus, R.; Makinson, R.; Minassian, A. M. Safety and Immunogenicity of the ChAdOx1 NCoV-19 Vaccine against SARS-CoV-2: A Preliminary Report of a Phase 1/2, Single-Blind, Randomised Controlled Trial. Lancet 2020, 396, 467– 478,  DOI: 10.1016/S0140-6736(20)31604-4
      23
      Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial
      Folegatti, Pedro M.; Ewer, Katie J.; Aley, Parvinder K.; Angus, Brian; Becker, Stephan; Belij-Rammerstorfer, Sandra; Bellamy, Duncan; Bibi, Sagida; Bittaye, Mustapha; Clutterbuck, Elizabeth A.; Dold, Christina; Faust, Saul N.; Finn, Adam; Flaxman, Amy L.; Hallis, Bassam; Heath, Paul; Jenkin, Daniel; Lazarus, Rajeka; Makinson, Rebecca; Minassian, Angela M.; Pollock, Katrina M.; Ramasamy, Maheshi; Robinson, Hannah; Snape, Matthew; Tarrant, Richard; Voysey, Merryn; Green, Catherine; Douglas, Alexander D.; Hill, Adrian V. S.; Lambe, Teresa; Gilbert, Sarah C.; Pollard, Andrew J.
      Lancet (2020), 396 (10249), 467-478CODEN: LANCAO; ISSN:0140-6736. (Elsevier Ltd.)
      The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) might be curtailed by vaccination. We assessed the safety, reactogenicity, and immunogenicity of a viral vectored coronavirus vaccine that expresses the spike protein of SARS-CoV-2. We did a phase 1/2, single-blind, randomised controlled trial in five trial sites in the UK of a chimpanzee adenovirus-vectored vaccine (ChAdOx1 nCoV-19) expressing the SARS-CoV-2 spike protein compared with a meningococcal conjugate vaccine (MenACWY) as control. Healthy adults aged 18-55 years with no history of lab. confirmed SARS-CoV-2 infection or of COVID-19-like symptoms were randomly assigned (1:1) to receive ChAdOx1 nCoV-19 at a dose of 5 x 1010 viral particles or MenACWY as a single i.m. injection. A protocol amendment in two of the five sites allowed prophylactic paracetamol to be administered before vaccination. Ten participants assigned to a non-randomised, unblinded ChAdOx1 nCoV-19 prime-boost group received a two-dose schedule, with the booster vaccine administered 28 days after the first dose. Humoral responses at baseline and following vaccination were assessed using a standardised total IgG ELISA against trimeric SARS-CoV-2 spike protein, a muliplexed immunoassay, three live SARS-CoV-2 neutralisation assays (a 50% plaque redn. neutralisation assay [PRNT50]; a microneutralisation assay [MNA50, MNA80, and MNA90]; and Marburg VN), and a pseudovirus neutralisation assay. Cellular responses were assessed using an ex-vivo interferon-γ enzyme-linked immunospot assay. The co-primary outcomes are to assess efficacy, as measured by cases of symptomatic virol. confirmed COVID-19, and safety, as measured by the occurrence of serious adverse events. Analyses were done by group allocation in participants who received the vaccine. Safety was assessed over 28 days after vaccination. Here, we report the preliminary findings on safety, reactogenicity, and cellular and humoral immune responses. The study is ongoing, and was registered at ISRCTN, 15281137, and ClinicalTrials.gov, NCT04324606. Between Apr. 23 and May 21, 2020, 1077 participants were enrolled and assigned to receive either ChAdOx1 nCoV-19 (n=543) or MenACWY (n=534), ten of whom were enrolled in the non-randomised ChAdOx1 nCoV-19 prime-boost group. Local and systemic reactions were more common in the ChAdOx1 nCoV-19 group and many were reduced by use of prophylactic paracetamol, including pain, feeling feverish, chills, muscle ache, headache, and malaise (all p<0·05). There were no serious adverse events related to ChAdOx1 nCoV-19. In the ChAdOx1 nCoV-19 group, spike-specific T-cell responses peaked on day 14 (median 856 spot-forming cells per million peripheral blood mononuclear cells, IQR 493-1802; n=43). Anti-spike IgG responses rose by day 28 (median 157 ELISA units [EU], 96-317; n=127), and were boosted following a second dose (639 EU, 360-792; n=10). Neutralising antibody responses against SARS-CoV-2 were detected in 32 (91%) of 35 participants after a single dose when measured in MNA80 and in 35 (100%) participants when measured in PRNT50. After a booster dose, all participants had neutralising activity (nine of nine in MNA80 at day 42 and ten of ten in Marburg VN on day 56). Neutralising antibody responses correlated strongly with antibody levels measured by ELISA (R2=0·67 by Marburg VN; p<0·001). ChAdOx1 nCoV-19 showed an acceptable safety profile, and homologous boosting increased antibody responses. These results, together with the induction of both humoral and cellular immune responses, support large-scale evaluation of this candidate vaccine in an ongoing phase 3 program.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhsVaku7fE&md5=4edd57b9d55d8a7c71ee84c8f62f7ca0
    24. 24
      Rouse, B. T.; Sehrawat, S. Immunity and Immunopathology to Viruses: What Decides the Outcome?. Nat. Rev. Immunol. 2010, 10, 514– 526,  DOI: 10.1038/nri2802
      24
      Immunity and immunopathology to viruses: what decides the outcome?
      Rouse, Barry T.; Sehrawat, Sharvan
      Nature Reviews Immunology (2010), 10 (7), 514-526CODEN: NRIABX; ISSN:1474-1733. (Nature Publishing Group)
      A review. Many viruses infect humans and most are controlled satisfactorily by the immune system with limited damage to host tissues. Some viruses, however, do cause overt damage to the host, either in isolated cases or as a reaction that commonly occurs after infection. The outcome is influenced by properties of the infecting virus, the circumstances of infection and several factors controlled by the host. In this Review, we focus on host factors that influence the outcome of viral infection, including genetic susceptibility, the age of the host when infected, the dose and route of infection, the induction of anti-inflammatory cells and proteins, as well as the presence of concurrent infections and past exposure to cross-reactive agents.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXnvFSgt78%253D&md5=a10d52b1ed35bea0d165b3cc88afd50b
    25. 25
      Klein, S. L.; Jedlicka, A.; Pekosz, A. The Xs and Y of Immune Responses to Viral Vaccines. Lancet Infect. Dis. 2010, 10, 338– 349,  DOI: 10.1016/S1473-3099(10)70049-9
      25
      The Xs and Y of immune responses to viral vaccines
      Klein, Sabra L.; Jedlicka, Anne; Pekosz, Andrew
      Lancet Infectious Diseases (2010), 10 (5), 338-349CODEN: LIDABP; ISSN:1473-3099. (Elsevier Ltd.)
      A review. Summary: The biol. differences assocd. with the sex of an individual are a major source of variation, affecting immune responses to vaccination. Compelling clin. data illustrate that men and women differ in their innate, humoral, and cell-mediated responses to viral vaccines. Sex affects the frequency and severity of adverse effects of vaccination, including fever, pain, and inflammation. Pregnancy can also substantially alter immune responses to vaccines. Data from clin. trials and animal models of vaccine efficacy lay the groundwork for future studies aimed at identifying the biol. mechanisms that underlie sex-specific responses to vaccines, including genetic and hormonal factors. An understanding and appreciation of the effect of sex and pregnancy on immune responses might change the strategies used by public health officials to start efficient vaccination programs (optimizing the timing and dose of the vaccine so that the max. no. of people are immunized), ensure sufficient levels of immune responses, minimize adverse effects, and allow for more efficient protection of populations that are high priority (eg, pregnant women and individuals with comorbid conditions).
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXht1WhsL7I&md5=581164b9d9113c651dc1901e737f6ffc
    26. 26
      Zhao, J.; Yuan, Q.; Wang, H.; Liu, W.; Liao, X.; Su, Y.; Wang, X.; Yuan, J.; Li, T.; Li, J.; Qian, S.; Hong, C.; Wang, F.; Liu, Y.; Wang, Z.; He, Q.; Li, Z.; He, B.; Zhang, T.; Fu, Y. Antibody Responses to SARS-CoV-2 in Patients of Novel Coronavirus Disease 2019. Clin. Infect. Dis. 2020,  DOI: 10.1093/cid/ciaa344
      There is no corresponding record for this reference.
    27. 27
      Chen, Z.; John Wherry, E. T Cell Responses in Patients with COVID-19. Nat. Rev. Immunol. 2020, 20, 529– 536,  DOI: 10.1038/s41577-020-0402-6
      27
      T cell responses in patients with COVID-19
      Chen, Zeyu; John Wherry, E.
      Nature Reviews Immunology (2020), 20 (9), 529-536CODEN: NRIABX; ISSN:1474-1733. (Nature Research)
      Abstr.: The role of T cells in the resoln. or exacerbation of COVID-19, as well as their potential to provide long-term protection from reinfection with SARS-CoV-2, remains debated. Nevertheless, recent studies have highlighted various aspects of T cell responses to SARS-CoV-2 infection that are starting to enable some general concepts to emerge.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhsVygtLvM&md5=2cf2f4b0bdf660e06e2574fbd505f32b
    28. 28
      Juno, J. A.; Tan, H.-X.; Lee, W. S.; Reynaldi, A.; Kelly, H. G.; Wragg, K.; Esterbauer, R.; Kent, H. E.; Batten, C. J.; Mordant, F. L.; Gherardin, N. A.; Pymm, P.; Dietrich, M. H.; Scott, N. E.; Tham, W.-H.; Godfrey, D. I.; Subbarao, K.; Davenport, M. P.; Kent, S. J.; Wheatley, A. K. Humoral and Circulating Follicular Helper T Cell Responses in Recovered Patients with COVID-19. Nat. Med. 2020, 26, 1428– 1434,  DOI: 10.1038/s41591-020-0995-0
      28
      Humoral and circulating follicular helper T cell responses in recovered patients with COVID-19
      Juno, Jennifer A.; Tan, Hyon-Xhi; Lee, Wen Shi; Reynaldi, Arnold; Kelly, Hannah G.; Wragg, Kathleen; Esterbauer, Robyn; Kent, Helen E.; Batten, C. Jane; Mordant, Francesca L.; Gherardin, Nicholas A.; Pymm, Phillip; Dietrich, Melanie H.; Scott, Nichollas E.; Tham, Wai-Hong; Godfrey, Dale I.; Subbarao, Kanta; Davenport, Miles P.; Kent, Stephen J.; Wheatley, Adam K.
      Nature Medicine (New York, NY, United States) (2020), 26 (9), 1428-1434CODEN: NAMEFI; ISSN:1078-8956. (Nature Research)
      Abstr.: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has dramatically expedited global vaccine development efforts1-3, most targeting the viral 'spike' glycoprotein (S). However, although prototypic S-based vaccines show promise in animal models12-14, the immunogenic properties of S in humans are poorly resolved. In this study, we characterized humoral and circulating follicular helper T cell (cTFH) immunity against spike in recovered patients with coronavirus disease 2019 (COVID-19). We found that S-specific antibodies, memory B cells and cTFH are consistently elicited after SARS-CoV-2 infection, demarking robust humoral immunity and pos. assocd. with plasma neutralizing activity. Comparatively low frequencies of B cells or cTFH specific for the receptor binding domain of S were elicited. Notably, the phenotype of S-specific cTFH differentiated subjects with potent neutralizing responses, providing a potential biomarker of potency for S-based vaccines entering the clinic. Overall, although patients who recovered from COVID-19 displayed multiple hallmarks of effective immune recognition of S, the wide spectrum of neutralizing activity obsd. suggests that vaccines might require strategies to selectively target the most potent neutralizing epitopes.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhtlynt7nE&md5=815451451dc3c9af0481599dd4f532ca
    29. 29
      Belongia, E. A.; Naleway, A. L. Smallpox Vaccine: The Good, the Bad, and the Ugly. Clin. Med. Res. 2003, 1, 87– 92,  DOI: 10.3121/cmr.1.2.87
      29
      Smallpox vaccine: the good, the bad, and the ugly
      Belongia Edward A; Naleway Allison L
      Clinical medicine & research (2003), 1 (2), 87-92 ISSN:1539-4182.
      Smallpox inarguably shaped the course of human history by killing countless millions in both the Old World and the New World. Dr. Edward Jenner's discovery of vaccination in the late 18th century, and the global eradication of smallpox in the 1970s, rank among the greatest achievements in human history. Amidst recent growing concerns about bioterrorism, smallpox vaccination has resurfaced from the history books to become a topic of major importance. Inoculation with vaccinia virus is highly effective for the prevention of smallpox infection, but it is associated with several known side effects that range from mild and self-limited to severe and life-threatening. As the United States moves forward with plans to vaccinate selected health care workers and the military, and perhaps offer the vaccination to all citizens in the future, it is important to fully understand and appreciate the history, risks, and benefits of smallpox vaccination.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BD2MritlKqug%253D%253D&md5=7e52639b593bb4c1a65d96186f3a8560
    30. 30
      Minor, P. D. An Introduction to Poliovirus: Pathogenesis, Vaccination, and the Endgame for Global Eradication. Methods Mol. Biol. 2016, 1387, 1– 10,  DOI: 10.1007/978-1-4939-3292-4_1
      30
      An introduction to poliovirus: pathogenesis, vaccination, and the endgame for global eradication
      Minor, Philip D.
      Methods in Molecular Biology (New York, NY, United States) (2016), 1387 (Poliovirus), 1-10CODEN: MMBIED; ISSN:1940-6029. (Springer)
      Poliomyelitis is caused by poliovirus, which is a pos. strand non-enveloped virus that occurs in three distinct serotypes (1, 2, and 3). Infection is mainly by the fecal-oral route and can be confi ned to the gut by antibodies induced either by vaccine, previous infection or maternally acquired. Vaccines include the live attenuated strains developed by Sabin and the inactivated vaccines developed by Salk; the live attenuated vaccine (Oral Polio Vaccine or OPV) has been the main tool in the Global Program of Polio eradication of the World Health Organization. Wild type 2 virus has not caused a case since 1999 and type 3 since 2012 and eradication seems near. However most infections are entirely silent so that sophisticated environmental surveillance may be needed to ensure that the virus has been eradicated, and the live vaccine can sometimes revert to virulent circulating forms under conditions that are not wholly understood. Cessation of vaccination is therefore an increasingly important issue and inactivated polio vaccine (IPV) is playing a larger part in the end game.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhs1yqsbvK&md5=bfd054dde95843357e97a98fa16f7871
    31. 31
      Gao, Y.; McKay, P. F.; Mann, J. F. S. Advances in HIV-1 Vaccine Development. Viruses 2018, 10, 167,  DOI: 10.3390/v10040167
      31
      Advances in HIV-1 vaccine development
      Gao, Yong; McKay, Paul F.; Mann, Jamie F. S.
      Viruses (2018), 10 (4), 167/1-167/26CODEN: VIRUBR; ISSN:1999-4915. (MDPI AG)
      A review. An efficacious HIV-1 vaccine is regarded as the best way to halt the ongoing HIV-1 epidemic. However, despite significant efforts to develop a safe and effective vaccine, the modestly protective RV144 trial remains the only efficacy trial to provide some level of protection against HIV-1 acquisition. This review will outline the history of HIV vaccine development, novel technologies being applied to HIV vaccinol. and immunogen design, as well as the studies that are ongoing to advance our understanding of vaccine-induced immune correlates of protection.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXisVWgtbnK&md5=c776907bb1c1afaa53e15409de8c1eaf
    32. 32
      Dudas, R. A.; Karron, R. A. Respiratory Syncytial Virus Vaccines. Clin. Microbiol. Rev. 1998, 11, 430– 439,  DOI: 10.1128/CMR.11.3.430
      32
      Respiratory syncytial virus vaccines
      Dudas R A; Karron R A
      Clinical microbiology reviews (1998), 11 (3), 430-9 ISSN:0893-8512.
      Respiratory syncytial virus (RSV) is the most important cause of viral lower respiratory tract illness (LRI) in infants and children worldwide and causes significant LRI in the elderly and in immunocompromised patients. The goal of RSV vaccination is to prevent serious RSV-associated LRI. There are several obstacles to the development of successful RSV vaccines, including the need to immunize very young infants, who may respond inadequately to vaccination; the existence of two antigenically distinct RSV groups, A and B; and the history of disease enhancement following administration of a formalin-inactivated vaccine. It is likely that more than one type of vaccine will be needed to prevent RSV LRI in the various populations at risk. Although vector delivery systems, synthetic peptide, and immune-stimulating complex vaccines have been evaluated in animal models, only the purified F protein (PFP) subunit vaccines and live attenuated vaccines have been evaluated in recent clinical trials. PFP-2 appears to be a promising vaccine for the elderly and for RSV-seropositive children with underlying pulmonary disease, whereas live cold-passaged (cp), temperature-sensitive (ts) RSV vaccines (denoted cpts vaccines) would most probably be useful in young infants. The availability of cDNA technology should allow further refinement of existing live attenuated cpts candidate vaccines to produce engineered vaccines that are satisfactorily attenuated, immunogenic, and phenotypically stable.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADyaK1czjtlKltA%253D%253D&md5=347f2f572c309e01d3e1c63e5cd80cd6
    33. 33
      Corthesy, B. Multi-Faceted Functions of Secretory IgA at Mucosal Surfaces. Front. Immunol. 2013,  DOI: 10.3389/fimmu.2013.00185
      There is no corresponding record for this reference.
    34. 34
      Chao, Y. X.; Rötzschke, O.; Tan, E.-K. The Role of IgA in COVID-19. Brain, Behav., Immun. 2020, 87, 182– 183,  DOI: 10.1016/j.bbi.2020.05.057
      34
      The role of IgA in COVID-19
      Chao, Yin Xia; Rotzschke, Olaf; Tan, Eng-King
      Brain, Behavior, and Immunity (2020), 87 (), 182-183CODEN: BBIMEW; ISSN:0889-1591. (Elsevier Inc.)
      Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 infection has affected close to 4 million people globally with more than 200,000 deaths and assocd. with various forms of morbidity and complications (Chan et al., 2020). The current virol. tests are either time consuming or of low sensitivity, which has serious implications on affected patients and general population. There is an urgent need for diagnostic tests so that effective treatment can be instituted. Secretory IgA plays a crucial role in the immune defense of mucosal surfaces, the first point of entry of SARS-CoV-2. IgA-based serol. tests targeting the SARS-CoV-2 specific Spike protein and nucleocapsid protein (NP) may thus represent an important diagnostic and therapeutic approach (Petherick, 2020; Okba et al., 2020).
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhtVels7vF&md5=f0bf38ea84bf54e7a092afa9ee73fccb
    35. 35
      Zhang, L.; Wang, W.; Wang, S. Effect of Vaccine Administration Modality on Immunogenicity and Efficacy. Expert Rev. Vaccines 2015, 14, 1509– 1523,  DOI: 10.1586/14760584.2015.1081067
      35
      Effect of vaccine administration modality on immunogenicity and efficacy
      Zhang, Lu; Wang, Wei; Wang, Shixia
      Expert Review of Vaccines (2015), 14 (11), 1509-1523CODEN: ERVXAX; ISSN:1476-0584. (Taylor & Francis Ltd.)
      The many factors impacting the efficacy of a vaccine can be broadly divided into three categories: features of the vaccine itself, including immunogen design, vaccine type, formulation, adjuvant and dosing; individual variations among vaccine recipients and vaccine administration-related parameters. While much literature exists related to vaccines, and recently systems biol. has started to dissect the impact of individual subject variation on vaccine efficacy, few studies have focused on the role of vaccine administration-related parameters on vaccine efficacy. Parenteral and mucosal vaccinations are traditional approaches for licensed vaccines; novel vaccine delivery approaches, including needless injection and adjuvant formulations, are being developed to further improve vaccine safety and efficacy. This review provides a brief summary of vaccine administration-related factors, including vaccination approach, delivery route and method of administration, to gain a better understanding of their potential impact on the safety and immunogenicity of candidate vaccines.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhslWgsL%252FN&md5=a293bb53c2f861b623d9f933f3124971
    36. 36
      Boyaka, P. N. Inducing Mucosal IgA: A Challenge for Vaccine Adjuvants and Delivery Systems. J. Immunol. 2017, 199, 9– 16,  DOI: 10.4049/jimmunol.1601775
      36
      Inducing Mucosal IgA: A Challenge for Vaccine Adjuvants and Delivery Systems
      Boyaka, Prosper N.
      Journal of Immunology (2017), 199 (1), 9-16CODEN: JOIMA3; ISSN:0022-1767. (American Association of Immunologists)
      Mucosal IgA or secretory IgA (SIgA) are structurally equipped to resist chem. degrdn. in the harsh environment of mucosal surfaces and enzymes of host or microbial origin. Prodn. of SIgA is finely regulated, and distinct T-independent and T-dependent mechanisms orchestrate Ig α class switching and SIgA responses against commensal and pathogenic microbes. Most infectious pathogens enter the host via mucosal surfaces. To provide a first line of protection at these entry ports, vaccines are being developed to induce pathogen-specific SIgA in addn. to systemic immunity achieved by injected vaccines. Mucosal or epicutaneous delivery of vaccines helps target the inductive sites for SIgA responses. The efficacy of such vaccines relies on the identification and/or engineering of vaccine adjuvants capable of supporting the development of SIgA alongside systemic immunity and delivery systems that improve vaccine delivery to the targeted anat. sites and immune cells.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhtVWmsb3N&md5=7b16d389486df37cdd7ca297e644649b
    37. 37
      Altimmune COVID-19 Vaccine Candidate Tested at UAB Shows Positive Preclinical Results - News. https://www.uab.edu/news/research/item/11426-altimmune-covid-19-vaccine-candidate-tested-at-uab-shows-positive-preclinical-results (accessed 2020-08-14).
      There is no corresponding record for this reference.
    38. 38
      OraPro-COVID-19. Home. https://www.stabilitech.com/orapro-covid-19/ (accessed 2020-08-14).
      There is no corresponding record for this reference.
    39. 39
      Quadram Researchers Working on COVID-19 Vaccine Join WHO Expert Groups. https://quadram.ac.uk/quadram-researchers-working-on-covid-19-vaccine-join-who-expert-groups/ (accessed Aug 14, 2020).
      There is no corresponding record for this reference.
    40. 40
      Zhang, Y.; Geng, X.; Tan, Y.; Li, Q.; Xu, C.; Xu, J.; Hao, L.; Zeng, Z.; Luo, X.; Liu, F.; Wang, H. New Understanding of the Damage of SARS-CoV-2 Infection Outside the Respiratory System. Biomed. Pharmacother. 2020, 127, 110195,  DOI: 10.1016/j.biopha.2020.110195
      40
      New understanding of the damage of SARS-CoV-2 infection outside the respiratory system
      Zhang, Yuhao; Geng, Xiuchao; Tan, Yanli; Li, Qiang; Xu, Can; Xu, Jianglong; Hao, Liangchao; Zeng, Zhaomu; Luo, Xianpu; Liu, Fulin; Wang, Hong
      Biomedicine & Pharmacotherapy (2020), 127 (), 110195CODEN: BIPHEX; ISSN:0753-3322. (Elsevier Masson SAS)
      A review. Since early Dec. 2019, a no. of pneumonia cases assocd. with unknown coronavirus infection were identified in Wuhan, China, and many addnl. cases were identified in other regions of China and in other countries within 3 mo. Currently, more than 80,000 cases have been diagnosed in China, including more than 3000 deaths. The epidemic is spreading to the rest of the world, posing a grave challenge to prevention and control. On Feb. 12, 2020, the International Committee on Taxonomy of Viruses and the World Health Organization officially named the novel coronavirus and assocd. pneumonia as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease 2019 (COVID-19), resp. According to the recent research on SARS-CoV-2, the virus mainly infects the respiratory system but may cause damage to other systems. In this paper, we will systematically review the pathogenic features, transmission routes, and infection mechanisms of SARS-CoV-2, as well as any adverse effects on the digestive system, urogenital system, central nervous system, and circulatory system, in order to provide a theor. and clin. basis for the diagnosis, classification, treatment, and prognosis assessment of SARS-CoV-2 infection.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXotlaqs7k%253D&md5=e32556c24767b83871721f5967ca2b17
    41. 41
      Kuba, K.; Imai, Y.; Penninger, J. M. Angiotensin-Converting Enzyme 2 in Lung Diseases. Curr. Opin. Pharmacol. 2006, 6, 271– 276,  DOI: 10.1016/j.coph.2006.03.001
      41
      Angiotensin-converting enzyme 2 in lung diseases
      Kuba, Keiji; Imai, Yumiko; Penninger, Josef M.
      Current Opinion in Pharmacology (2006), 6 (3), 271-276CODEN: COPUBK; ISSN:1471-4892. (Elsevier Ltd.)
      A review. The renin-angiotensin system (RAS) plays a key role in maintaining blood pressure homeostasis, as well as fluid and salt balance. Angiotensin II, a key effector peptide of the system, causes vasoconstriction and exerts multiple biol. functions. Angiotensin-converting enzyme (ACE) plays a central role in generating angiotensin II from angiotensin I, and capillary blood vessels in the lung are one of the major sites of ACE expression and angiotensin II prodn. in the human body. The RAS has been implicated in the pathogenesis of pulmonary hypertension and pulmonary fibrosis, both commonly seen in chronic lung diseases such as chronic obstructive lung disease. Recent studies indicate that the RAS also plays a crit. role in acute lung diseases, esp. acute respiratory distress syndrome (ARDS). ACE2, a close homolog of ACE, functions as a neg. regulator of the angiotensin system and was identified as a key receptor for SARS (severe acute respiratory syndrome) coronavirus infections. In the lung, ACE2 protects against acute lung injury in several animal models of ARDS. Thus, the RAS appears to play a crit. role in the pathogenesis of acute lung injury. Indeed, increasing ACE2 activity might be a novel approach for the treatment of acute lung failure in several diseases.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD28XksFynu7c%253D&md5=ee10aae36a7af1b675149f411db37d72
    42. 42
      Xia, H.; Lazartigues, E. Angiotensin-converting Enzyme 2 in the Brain: Properties and Future Directions. J. Neurochem. 2008, 107, 1482– 1494,  DOI: 10.1111/j.1471-4159.2008.05723.x
      42
      Angiotensin-converting enzyme 2 in the brain: properties and future directions
      Xia, Huijing; Lazartigues, Eric
      Journal of Neurochemistry (2008), 107 (6), 1482-1494CODEN: JONRA9; ISSN:0022-3042. (Wiley-Blackwell)
      A review. Angiotensin (Ang)-converting enzyme (ACE) 2 cleaves Ang-II into the vasodilator peptide Ang-(1-7), thus acting as a pivotal element in balancing the local effects of these peptides. ACE2 has been identified in various tissues and is supposed to be a modulator of cardiovascular function. Decreases in ACE2 expression and activity have been reported in models of hypertension, heart failure, atherosclerosis, diabetic nephropathy and others. In addn., the expression level and/or activity are affected by other renin-angiotensin system components (e.g., ACE and AT1 receptors). Local inhibition or global deletion of brain ACE2 induces a redn. in baroreflex sensitivity. Moreover, ACE2-null mice have been shown to exhibit either blood pressure or cardiac dysfunction phenotypes. On the other hand, over-expression of ACE2 exerts protective effects in local tissues, including the brain. In this review, we will first summarize the major findings linking ACE2 to cardiovascular function in the periphery then focus on recent discoveries related to ACE2 in the CNS. Finally, we will unveil new tools designed to address the importance of central ACE2 in various diseases, and discuss the potential for this carboxypeptidase as a new target in the treatment of hypertension and other cardiovascular diseases.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXis1Sksg%253D%253D&md5=b497b1111e6aac23f5d992a5548a65b6
    43. 43
      Wang, J.; Zhao, S.; Liu, M.; Zhao, Z.; Xu, Y.; Wang, P.; Lin, M.; Xu, Y.; Huang, B.; Zuo, X.; Chen, Z.; Bai, F.; Cui, J.; Lew, A. M.; Zhao, J.; Zhang, Y.; Luo, H.; Zhang, Y. ACE2 Expression by Colonic Epithelial Cells Is Associated with Viral Infection, Immunity and Energy Metabolism. medRxiv 2020, 2020.02.05.20020545. https://www.medrxiv.org/content/10.1101/2020.02.05.20020545v1 (accessed 2020-08-06).
      There is no corresponding record for this reference.
    44. 44
      Charles A Janeway, J.; Travers, P.; Walport, M.; Shlomchik, M. J. The Distribution and Functions of Immunoglobulin Isotypes. Immunobiology: The Immune System in Health and Disease, 5; Garland Science: New York, 2001.
      There is no corresponding record for this reference.
    45. 45
      Gilbert, S. C. T-Cell-Inducing Vaccines – What’s the Future. Immunology 2012, 135, 19– 26,  DOI: 10.1111/j.1365-2567.2011.03517.x
      45
      T-cell-inducing vaccines - what's the future
      Gilbert, Sarah C.
      Immunology (2012), 135 (1), 19-26CODEN: IMMUAM; ISSN:0019-2805. (Wiley-Blackwell)
      A review. In the twentieth century vaccine development has moved from the use of attenuated or killed micro-organisms to protein sub-unit vaccines, with vaccine immunogenicity assessed by measuring antibodies induced by vaccination. However, for many infectious diseases T cells are an important part of naturally acquired protective immune responses, and inducing these by vaccination has been the aim of much research. The progress that has been made in developing effective T-cell-inducing vaccines against viral and parasitic diseases such as HIV and malaria is discussed, along with recent developments in therapeutic vaccine development for chronic viral infections and cancer. Although many ways of inducing T cells by vaccination have been assessed, the majority result in low level, non-protective responses. Sufficient clin. research has now been conducted to establish that replication-deficient viral vectored vaccines lead the field in inducing strong and broad responses, and efficacy studies of T-cell-inducing vaccines against a no. of diseases are finally demonstrating that this is a valid approach to filling the gaps in our defense against not only infectious disease, but some forms of cancer.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXhs12ntLzO&md5=ea972d5f9096b5d53dcc6931f58b74ae
    46. 46
      Todryk, S. M. T Cell Memory to Vaccination. Vaccines (Basel, Switz.) 2018, 6, 84,  DOI: 10.3390/vaccines6040084
      46
      T cell memory to vaccination
      Todryk, Stephen M.
      Vaccines (Basel, Switzerland) (2018), 6 (4), 84CODEN: VBSABP; ISSN:2076-393X. (MDPI AG)
      Most immune responses assocd. with vaccination are controlled by specific T cells of a CD4+ helper phenotype which mediate the generation of effector antibodies, cytotoxic T lymphocytes (CTLs), or the activation of innate immune effector cells. A rapidly growing understanding of the generation, maintenance, activity, and measurement of such T cells is leading to vaccination strategies with greater efficacy and potentially greater microbial coverage.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXktFyitLo%253D&md5=d9f50554bedadd53188e891278bd91d7
    47. 47
      Lange, H.; Hecht, O.; Zemlin, M.; Trad, A.; Tanasa, R. I.; Schroeder, H. W.; Lemke, H. Immunoglobulin Class Switching Appears to Be Regulated by B Cell Antigen Receptor-Specific T Cell Action. Eur. J. Immunol. 2012, 42, 1016– 1029,  DOI: 10.1002/eji.201141857
      47
      Immunoglobulin class switching appears to be regulated by B-cell antigen receptor-specific T-cell action
      Lange, Hans; Hecht, Oliver; Zemlin, Michael; Trad, Ahmad; Tanasa, Radu I.; Schroeder, Harry W.; Lemke, Hilmar
      European Journal of Immunology (2012), 42 (4), 1016-1029CODEN: EJIMAF; ISSN:0014-2980. (Wiley-VCH Verlag GmbH & Co. KGaA)
      Antigen affinity is commonly viewed as the driving force behind the selection for dominant clonotypes that can occur during the T-cell-dependent processes of class switch recombination (CSR) and immune maturation. To test this view, we analyzed the variable gene repertoires of natural monoclonal antibodies to the hapten 2-phenyloxazolone (phOx) as well as those generated after phOx protein carrier-induced thymus-dependent or Ficoll-induced thymus-independent antigen stimulation. In contrast to expectations, the extent of IgM heterogeneity proved similar and many IgM from these three populations exhibited similar or even greater affinities than the classic Ox1 clonotype that dominates only after CSR among primary and memory IgG. The population of clones that were selected during CSR exhibited a reduced VH/VL repertoire that was enriched for variable domains with shorter and more uniform CDR-H3 lengths and almost completely stripped of variable domains encoded by the large VH1 family. Thus, contrary to the current paradigm, T-cell-dependent clonal selection during CSR appeared to select for VH family and CDR-H3 loop content even when the affinity provided by alternative clones exhibited similar to increased affinity for antigen.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XmtVKrtL8%253D&md5=18f6f00ff3f75581637e645e026dd4f6
    48. 48
      Lin, Q.; Zhu, L.; Ni, Z.; Meng, H.; You, L. Duration of Serum Neutralizing Antibodies for SARS-CoV-2: Lessons from SARS-CoV Infection. J. Microbiol., Immunol. Infect. 2020, 53, 821,  DOI: 10.1016/j.jmii.2020.03.015
      48
      Duration of serum neutralizing antibodies for SARS-CoV-2: Lessons from SARS-CoV infection
      Lin, Qingqing; Zhu, Li; Ni, Zuowei; Meng, Haitao; You, Liangshun
      Journal of Microbiology, Immunology and Infection (2020), 53 (5), 821-822CODEN: JMIIFG; ISSN:1995-9133. (Elsevier Taiwan LLC)
      The authors examine the reports of protection afforded by specific antibodies in convalescent SARS-CoV patients. The finding suggested that the immune responses of specific Abs were maintained in more than 90% of recovered SARS-CoV patients for 2 years.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXlvFyrtb4%253D&md5=70eaa8a770a0674ba8fe02a9398a59e0
    49. 49
      Clinical Stage Pipeline – Novavax – Creating Tomorrow’s Vaccines Today. Novavax.com. https://novavax.com/our-pipeline#nvx-cov2373 (accessed 2020-08-14).
      There is no corresponding record for this reference.
    50. 50
      Coffman, R. L.; Sher, A.; Seder, R. A. Vaccine Adjuvants: Putting Innate Immunity to Work. Immunity 2010, 33, 492– 503,  DOI: 10.1016/j.immuni.2010.10.002
      50
      Vaccine Adjuvants: Putting Innate Immunity to Work
      Coffman, Robert L.; Sher, Alan; Seder, Robert A.
      Immunity (2010), 33 (4), 492-503CODEN: IUNIEH; ISSN:1074-7613. (Cell Press)
      A review. Adjuvants enhance immunity to vaccines and exptl. antigens by a variety of mechanisms. In the past decade, many receptors and signaling pathways in the innate immune system have been defined and these innate responses strongly influence the adaptive immune response. The focus of this review is to delineate the innate mechanisms by which adjuvants mediate their effects. We highlight how adjuvants can be used to influence the magnitude and alter the quality of the adaptive response in order to provide max. protection against specific pathogens. Despite the impressive success of currently approved adjuvants for generating immunity to viral and bacterial infections, there remains a need for improved adjuvants that enhance protective antibody responses, esp. in populations that respond poorly to current vaccines. However, the larger challenge is to develop vaccines that generate strong T cell immunity with purified or recombinant vaccine antigens.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXhtlGmtLvF&md5=26e53f025adef76f6446093b935c52b3
    51. 51
      McKee, A. S.; MacLeod, M. K. L.; Kappler, J. W.; Marrack, P. Immune Mechanisms of Protection: Can Adjuvants Rise to the Challenge?. BMC Biol. 2010, 8, 37,  DOI: 10.1186/1741-7007-8-37
      51
      Immune mechanisms of protection: can adjuvants rise to the challenge?
      McKee Amy S; MacLeod Megan K L; Kappler John W; Marrack Philippa
      BMC biology (2010), 8 (), 37 ISSN:.
      For many diseases vaccines are lacking or only partly effective. Research on protective immunity and adjuvants that generate vigorous immune responses may help generate effective vaccines against such pathogens.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC3c3lsFGrsg%253D%253D&md5=5e16bce0994434d63890142ac358e987
    52. 52
      Kreutz, M.; Giquel, B.; Hu, Q.; Abuknesha, R.; Uematsu, S.; Akira, S.; Nestle, F. O.; Diebold, S. S. Antibody-Antigen-Adjuvant Conjugates Enable Co-Delivery of Antigen and Adjuvant to Dendritic Cells in Cis but Only Have Partial Targeting Specificity. PLoS One 2012, 7, e40208  DOI: 10.1371/journal.pone.0040208
      52
      Antibody-antigen-adjuvant conjugates enable co-delivery of antigen and adjuvant to dendritic cells in cis but only have partial targeting specificity
      Kreutz, Martin; Giquel, Benoit; Hu, Qin; Abuknesha, Ram; Uematsu, Satoshi; Akira, Shizuo; Nestle, Frank O.; Diebold, Sandra S.
      PLoS One (2012), 7 (7), e40208CODEN: POLNCL; ISSN:1932-6203. (Public Library of Science)
      Antibody-antigen conjugates, which promote antigen-presentation by dendritic cells (DC) by means of targeted delivery of antigen to particular DC subsets, represent a powerful vaccination approach. To ensure immunity rather than tolerance induction the co-administration of a suitable adjuvant is paramount. However, co-administration of unlinked adjuvant cannot ensure that all cells targeted by the antibody conjugates are appropriately activated. Furthermore, antigen-presenting cells (APC) that do not present the desired antigen are equally strongly activated and could prime undesired responses against self-antigens. We, therefore, were interested in exploring targeted co-delivery of antigen and adjuvant in cis in form of antibody-antigen-adjuvant conjugates for the induction of anti-tumor immunity. In this study, we report on the assembly and characterization of conjugates consisting of DEC205-specific antibody, the model antigen ovalbumin (OVA) and CpG oligodeoxynucleotides (ODN). We show that such conjugates are more potent at inducing cytotoxic T lymphocyte (CTL) responses than control conjugates mixed with sol. CpG. However, our study also reveals that the nucleic acid moiety of such antibody-antigen-adjuvant conjugates alters their binding and uptake and allows delivery of the antigen and the adjuvant to cells partially independently of DEC205. Nevertheless, antibody-antigen-adjuvant conjugates are superior to antibody-free antigen-adjuvant conjugates in priming CTL responses and efficiently induce anti-tumor immunity in the murine B16 pseudo-metastasis model. A better understanding of the role of the antibody moiety is required to inform future conjugate vaccination strategies for efficient induction of anti-tumor responses.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhtVGmtrfM&md5=142120e1e276f1600da9d5b018759397
    53. 53
      Wang, Z.-B.; Xu, J. Better Adjuvants for Better Vaccines: Progress in Adjuvant Delivery Systems, Modifications, and Adjuvant–Antigen Codelivery. Vaccines (Basel, Switz.) 2020, 8, 128,  DOI: 10.3390/vaccines8010128
      53
      Better adjuvants for better vaccines: progress in adjuvant delivery systems, modifications, and adjuvant-antigen codelivery
      Wang, Zhi-Biao; Xu, Jing
      Vaccines (Basel, Switzerland) (2020), 8 (1), 128CODEN: VBSABP; ISSN:2076-393X. (MDPI AG)
      Traditional aluminum adjuvants can trigger strong humoral immunity but weak cellular immunity, limiting their application in some vaccines. Currently, various immunomodulators and delivery carriers are used as adjuvants, and the mechanisms of action of some of these adjuvants are clear. However, customizing targets of adjuvant action (cellular or humoral immunity) and action intensity (enhancement or inhibition) according to different antigens selected is time-consuming. Here, we review the adjuvant effects of some delivery systems and immune stimulants. In addn., to improve the safety, effectiveness, and accessibility of adjuvants, new trends in adjuvant development and their modification strategies are discussed.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhsVChsLjN&md5=a95c03fb6a20afd40a3b2695738b6ac1
    54. 54
      Pati, R.; Shevtsov, M.; Sonawane, A. Nanoparticle Vaccines against Infectious Diseases. Front. Immunol. 2018,  DOI: 10.3389/fimmu.2018.02224
      There is no corresponding record for this reference.
    55. 55
      Chattopadhyay, S.; Chen, J.-Y.; Chen, H.-W.; Hu, C.-M. J. Nanoparticle Vaccines Adopting Virus-Like Features for Enhanced Immune Potentiation. Nanotheranostics 2017, 1, 244– 260,  DOI: 10.7150/ntno.19796
      55
      Nanoparticle Vaccines Adopting Virus-like Features for Enhanced Immune Potentiation
      Chattopadhyay Saborni; Chen Jui-Yi; Hu Che-Ming Jack; Chattopadhyay Saborni; Chen Hui-Wen; Chen Hui-Wen; Hu Che-Ming Jack
      Nanotheranostics (2017), 1 (3), 244-260 ISSN:.
      Synthetic nanoparticles play an increasingly significant role in vaccine design and development as many nanoparticle vaccines show improved safety and efficacy over conventional formulations. These nanoformulations are structurally similar to viruses, which are nanoscale pathogenic organisms that have served as a key selective pressure driving the evolution of our immune system. As a result, mechanisms behind the benefits of nanoparticle vaccines can often find analogue to the interaction dynamics between the immune system and viruses. This review covers the advances in vaccine nanotechnology with a perspective on the advantages of virus mimicry towards immune potentiation. It provides an overview to the different types of nanomaterials utilized for nanoparticle vaccine development, including functionalization strategies that bestow nanoparticles with virus-like features. As understanding of human immunity and vaccine mechanisms continue to evolve, recognizing the fundamental semblance between synthetic nanoparticles and viruses may offer an explanation for the superiority of nanoparticle vaccines over conventional vaccines and may spur new design rationales for future vaccine research. These nanoformulations are poised to provide solutions towards pressing and emerging human diseases.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC1M7ks1SgsA%253D%253D&md5=b2fc2f2c624f586c8bd909a64a00501d
    56. 56
      Wrapp, D.; Wang, N.; Corbett, K. S.; Goldsmith, J. A.; Hsieh, C.-L.; Abiona, O.; Graham, B. S.; McLellan, J. S. Cryo-EM Structure of the 2019-NCoV Spike in the Prefusion Conformation. Science 2020, 367, 1260– 1263,  DOI: 10.1126/science.abb2507
      56
      Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation
      Wrapp, Daniel; Wang, Nianshuang; Corbett, Kizzmekia S.; Goldsmith, Jory A.; Hsieh, Ching-Lin; Abiona, Olubukola; Graham, Barney S.; McLellan, Jason S.
      Science (Washington, DC, United States) (2020), 367 (6483), 1260-1263CODEN: SCIEAS; ISSN:1095-9203. (American Association for the Advancement of Science)
      The outbreak of a novel coronavirus (2019-nCoV) represents a pandemic threat that has been declared a public health emergency of international concern. The CoV spike (S) glycoprotein is a key target for vaccines, therapeutic antibodies, and diagnostics. To facilitate medical countermeasure development, we detd. a 3.5-angstrom-resoln. cryo-electron microscopy structure of the 2019-nCoV S trimer in the prefusion conformation. The predominant state of the trimer has one of the three receptor-binding domains (RBDs) rotated up in a receptor-accessible conformation. We also provide biophys. and structural evidence that the 2019-nCoV S protein binds angiotensin-converting enzyme 2 (ACE2) with higher affinity than does severe acute respiratory syndrome (SARS)-CoV S. Addnl., we tested several published SARS-CoV RBD-specific monoclonal antibodies and found that they do not have appreciable binding to 2019-nCoV S, suggesting that antibody cross-reactivity may be limited between the two RBDs. The structure of 2019-nCoV S should enable the rapid development and evaluation of medical countermeasures to address the ongoing public health crisis.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXkvFemt70%253D&md5=27d08cbb9a43d1da051a8a92a9f68aa5
    57. 57
      Kanekiyo, M.; Joyce, M. G.; Gillespie, R. A.; Gallagher, J. R.; Andrews, S. F.; Yassine, H. M.; Wheatley, A. K.; Fisher, B. E.; Ambrozak, D. R.; Creanga, A.; Leung, K.; Yang, E. S.; Boyoglu-Barnum, S.; Georgiev, I. S.; Tsybovsky, Y.; Prabhakaran, M. S.; Andersen, H.; Kong, W.-P.; Baxa, U.; Zephir, K. L. Mosaic Nanoparticle Display of Diverse Influenza Virus Hemagglutinins Elicits Broad B Cell Responses. Nat. Immunol. 2019, 20, 362– 372,  DOI: 10.1038/s41590-018-0305-x
      57
      Mosaic nanoparticle display of diverse influenza virus hemagglutinins elicits broad B cell responses
      Kanekiyo, Masaru; Joyce, M. Gordon; Gillespie, Rebecca A.; Gallagher, John R.; Andrews, Sarah F.; Yassine, Hadi M.; Wheatley, Adam K.; Fisher, Brian E.; Ambrozak, David R.; Creanga, Adrian; Leung, Kwanyee; Yang, Eun Sung; Boyoglu-Barnum, Seyhan; Georgiev, Ivelin S.; Tsybovsky, Yaroslav; Prabhakaran, Madhu S.; Andersen, Hanne; Kong, Wing-Pui; Baxa, Ulrich; Zephir, Kathryn L.; Ledgerwood, Julie E.; Koup, Richard A.; Kwong, Peter D.; Harris, Audray K.; McDermott, Adrian B.; Mascola, John R.; Graham, Barney S.
      Nature Immunology (2019), 20 (3), 362-372CODEN: NIAMCZ; ISSN:1529-2908. (Nature Research)
      The present vaccine against influenza virus has the inevitable risk of antigenic discordance between the vaccine and the circulating strains, which diminishes vaccine efficacy. This necessitates new approaches that provide broader protection against influenza. Here we designed a vaccine using the hypervariable receptor-binding domain (RBD) of viral hemagglutinin displayed on a nanoparticle (np) able to elicit antibody responses that neutralize H1N1 influenza viruses spanning over 90 years. Co-display of RBDs from multiple strains across time, so that the adjacent RBDs are heterotypic, provides an avidity advantage to cross-reactive B cells. Immunization with the mosaic RBD-np elicited broader antibody responses than those induced by an admixt. of nanoparticles encompassing the same set of RBDs as sep. homotypic arrays. Furthermore, we identified a broadly neutralizing monoclonal antibody in a mouse immunized with mosaic RBD-np. The mosaic antigen array signifies a unique approach that subverts monotypic immunodominance and allows otherwise subdominant cross-reactive B cell responses to emerge.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXmtFKktrw%253D&md5=ac54fd5220413d1d6d478228830b4d1c
    58. 58
      Cueni, L. N.; Detmar, M. The Lymphatic System in Health and Disease. Lymphatic Res. Biol. 2008, 6, 109– 122,  DOI: 10.1089/lrb.2008.1008
      58
      The lymphatic system in health and disease
      Cueni Leah N; Detmar Michael
      Lymphatic research and biology (2008), 6 (3-4), 109-22 ISSN:1539-6851.
      The lymphatic vascular system has an important role in the regulation of tissue pressure, immune surveillance and the absorption of dietary fat in the intestine. There is growing evidence that the lymphatic system also contributes to a number of diseases, such as lymphedema, cancer metastasis and different inflammatory disorders. The discovery of various molecular markers allowing the distinction of blood and lymphatic vessels, together with the availability of a increasing number of in vitro and in vivo models to study various aspects of lymphatic biology, has enabled tremendous progress in research into the development and function of the lymphatic system. This review discusses recent advances in our understanding of the embryonic development of the lymphatic vasculature, the molecular mechanisms mediating lymphangiogenesis in the adult, the role of lymphangiogenesis in chronic inflammation and lymphatic cancer metastasis, and the emerging importance of the lymphatic vasculature as a therapeutic target.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BD1M%252FjvFKksA%253D%253D&md5=8fd29107de0b47951255215a40ec5054
    59. 59
      Cai, S.; Zhang, Q.; Bagby, T.; Forrest, M. L. Lymphatic Drug Delivery Using Engineered Liposomes and Solid Lipid Nanoparticles. Adv. Drug Delivery Rev. 2011, 63, 901– 908,  DOI: 10.1016/j.addr.2011.05.017
      59
      Lymphatic drug delivery using engineered liposomes and solid lipid nanoparticles
      Cai, Shuang; Yang, Qiuhong; Bagby, Taryn R.; Forrest, M. Laird
      Advanced Drug Delivery Reviews (2011), 63 (10-11), 901-908CODEN: ADDREP; ISSN:0169-409X. (Elsevier B.V.)
      A review. The lymphatic system plays a crucial role in the immune system's recognition and response to disease, and most solid cancers initially spread from the primary site via the tumor's surrounding lymphatics before hematol. dissemination. Hence, the lymphatic system is an important target for developing new vaccines, cancer treatments, and diagnostic agents. Targeting the lymphatic system by s.c., intestinal, and pulmonary routes was evaluated and subsequently utilized to improve lymphatic penetration and retention of drug mols., reduce drug-related systemic toxicities, and enhance bioavailability of poorly sol. and unstable drugs. Lymphatic imaging is an essential tool for the detection and staging of cancer. New nano-based technologies offer improved detection and characterization of the nodal diseases, while new delivery devices can better target and confine treatments to tumors within the nodal space while sparing healthy tissues. This manuscript reviews recent advances in the field of lymphatic drug delivery and imaging and focuses specifically on the development of liposomes and solid lipid nanoparticles for lymphatic introduction via the s.c., intestinal, and pulmonary routes.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXhtV2ntbjM&md5=17ebde4cabf30b63e36e8333025d2823
    60. 60
      eTheRNA Launches an International Consortium and Starts Development of Cross-Strain Protective CoV-2 mRNA Vaccine for High Risk Populations. https://finance.yahoo.com/news/etherna-launches-international-consortium-starts-080000668.html (accessed 2020-09-16).
      There is no corresponding record for this reference.
    61. 61
      B.V, I. Intravacc Partners with Wageningen Bioveterinary Research and Utrecht University to Develop an Intranasal COVID-19 Vaccine. https://www.prnewswire.com/news-releases/intravacc-partners-with-wageningen-bioveterinary-research-and-utrecht-university-to-develop-an-intranasal-covid-19-vaccine-301070721.html (accessed 2020-09-16).
      There is no corresponding record for this reference.
    62. 62
      Shin, M. D.; Shukla, S.; Chung, Y. H.; Beiss, V.; Chan, S. K.; Ortega-Rivera, O. A.; Wirth, D. M.; Chen, A.; Sack, M.; Pokorski, J. K.; Steinmetz, N. F. COVID-19 Vaccine Development and a Potential Nanomaterial Path Forward. Nat. Nanotechnol. 2020, 15, 646– 655,  DOI: 10.1038/s41565-020-0737-y
      62
      COVID-19 vaccine development and a potential nanomaterial path forward
      Shin, Matthew D.; Shukla, Sourabh; Chung, Young Hun; Beiss, Veronique; Chan, Soo Khim; Ortega-Rivera, Oscar A.; Wirth, David M.; Chen, Angela; Sack, Markus; Pokorski, Jonathan K.; Steinmetz, Nicole F.
      Nature Nanotechnology (2020), 15 (8), 646-655CODEN: NNAABX; ISSN:1748-3387. (Nature Research)
      A review. Abstr.: The COVID-19 pandemic has infected millions of people with no clear signs of abatement owing to the high prevalence, long incubation period and lack of established treatments or vaccines. Vaccines are the most promising soln. to mitigate new viral strains. The genome sequence and protein structure of the 2019-novel coronavirus (nCoV or SARS-CoV-2) were made available in record time, allowing the development of inactivated or attenuated viral vaccines along with subunit vaccines for prophylaxis and treatment. Nanotechnol. benefits modern vaccine design since nanomaterials are ideal for antigen delivery, as adjuvants, and as mimics of viral structures. In fact, the first vaccine candidate launched into clin. trials is an mRNA vaccine delivered via lipid nanoparticles. To eradicate pandemics, present and future, a successful vaccine platform must enable rapid discovery, scalable manufg. and global distribution. Here, we review current approaches to COVID-19 vaccine development and highlight the role of nanotechnol. and advanced manufg.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhsVSju73L&md5=7e381a11e739e763f63bd0ff3e5c3a07
    63. 63
      Milken Institute’s COVID-19 Treatment and Vaccine Tracker Tracks the Development of Treatments and Vaccines for COVID-19. https://covid-19tracker.milkeninstitute.org/ (accessed 2020-08-03).
      There is no corresponding record for this reference.
    64. 64
      Delrue, I.; Verzele, D.; Madder, A.; Nauwynck, H. J. Inactivated Virus Vaccines from Chemistry to Prophylaxis: Merits, Risks and Challenges. Expert Rev. Vaccines 2012, 11, 695– 719,  DOI: 10.1586/erv.12.38
      64
      Inactivated virus vaccines from chemistry to prophylaxis: merits, risks and challenges
      Delrue, Iris; Verzele, Dieter; Madder, Annemieke; Nauwynck, Hans J.
      Expert Review of Vaccines (2012), 11 (6), 695-719CODEN: ERVXAX; ISSN:1476-0584. (Expert Reviews Ltd.)
      The aim of this review is to make researchers aware of the benefits of an efficient quality control system for prediction of a developed vaccine's efficacy. Two major goals should be addressed when inactivating a virus for vaccine purposes: first, the infectious virus should be inactivated completely in order to be safe, and second, the viral epitopes important for the induction of protective immunity should be conserved after inactivation in order to have an antigen of high quality. Therefore, some problems assocd. with the virus inactivation process, such as virus aggregate formation, protein crosslinking, protein denaturation and degrdn. should be addressed before testing an inactivated vaccine in vivo.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhtFKjurrN&md5=7b3125e1681156508660c1b6e9cb014f
    65. 65
      Pulendran, B.; Ahmed, R. Immunological Mechanisms of Vaccination. Nat. Immunol. 2011, 12, 509– 517,  DOI: 10.1038/ni.2039
      65
      Immunological mechanisms of vaccination
      Pulendran, Bali; Ahmed, Rafi
      Nature Immunology (2011), 12 (6), 509-517CODEN: NIAMCZ; ISSN:1529-2908. (Nature Publishing Group)
      A review. Vaccines represent one of the greatest triumphs of modern medicine. Despite the common origins of vaccinol. and immunol. more than 200 years ago, the two disciplines have evolved along such different trajectories that most of the highly successful vaccines have been made empirically, with little or no immunol. insight. Recent advances in innate immunity have offered new insights about the mechanisms of vaccine-induced immunity and have facilitated a more rational approach to vaccine design. Here we will discuss these advances and emerging themes on the immunol. of vaccination.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXmtF2lu7o%253D&md5=09eeeb323fd6c819c4939eaf7cb69761
    66. 66
      Vartak, A.; Sucheck, S. J. Recent Advances in Subunit Vaccine Carriers. Vaccines (Basel, Switz.) 2016, 4, 12,  DOI: 10.3390/vaccines4020012
      66
      Recent advances in subunit vaccine carriers
      Vartak, Abhishek; Sucheck, Steven J.
      Vaccines (Basel, Switzerland) (2016), 4 (2), 12/1-12/18CODEN: VBSABP; ISSN:2076-393X. (MDPI AG)
      The lower immunogenicity of synthetic subunit antigens, compared to live attenuated vaccines, is being addressed with improved vaccine carriers. Recent reports indicate that the physio-chem. properties of these carriers can be altered to achieve optimal antigen presentation, endosomal escape, particle bio-distribution, and cellular trafficking. The carriers can be modified with various antigens and ligands for dendritic cells targeting. They can also be modified with adjuvants, either covalently or entrapped in the matrix, to improve cellular and humoral immune responses against the antigen. As a result, these multi-functional carrier systems are being explored for use in active immunotherapy against cancer and infectious diseases. Advancing technol., improved anal. methods, and use of computational methodol. have also contributed to the development of subunit vaccine carriers. This review details recent breakthroughs in the design of nano-particulate vaccine carriers, including liposomes, polymeric nanoparticles, and inorg. nanoparticles.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXnvF2mtbg%253D&md5=16f5079047f303f38533eca9e0e2e653
    67. 67
      Vogel, F. R.; Sarver, N. Nucleic Acid Vaccines. Clin. Microbiol. Rev. 1995, 8, 406– 410,  DOI: 10.1128/CMR.8.3.406
      67
      Nucleic acid vaccines
      Vogel, Frederick R.; Sarver, Nava
      Clinical Microbiology Reviews (1995), 8 (3), 406-10CODEN: CMIREX; ISSN:0893-8512. (American Society for Microbiology)
      A review, with 32 refs. The authors discuss nucleic acid vaccines development, DNA vaccines against retroviruses, retrovirus-mediated gene transfer, parameters affecting gene expression and immunogenicity of DNA vaccines, safety considerations for nucleic acid vaccines, and RNA vaccines.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK2MXnt1OqsLg%253D&md5=ae1b5593aa383168bf3df775fcfcae3a
    68. 68
      Choi, Y.; Chang, J. Viral Vectors for Vaccine Applications. Clin. Exp. Vaccine Res. 2013, 2, 97– 105,  DOI: 10.7774/cevr.2013.2.2.97
      68
      Viral vectors for vaccine applications
      Choi, Youngjoo; Chang, Jun
      Clinical and Experimental Vaccine Research (2013), 2 (2), 97-105CODEN: CEVRA4; ISSN:2287-3651. (Korean Vaccine Society)
      A review. Traditional approach of inactivated or live-attenuated vaccine immunization has resulted in impressive success in the redn. and control of infectious disease outbreaks. However, many pathogens remain less amenable to deal with the traditional vaccine strategies, and more appropriate vaccine strategy is in need. Recent discoveries that led to increased understanding of viral mol. biol. and genetics has rendered the used of viruses as vaccine platforms and as potential anti-cancer agents. Due to their ability to effectively induce both humoral and cell-mediated immune responses, viral vectors are deemed as an attractive alternative to the traditional platforms to deliver vaccine antigens as well as to specifically target and kill tumor cells. With potential targets ranging from cancers to a vast no. of infectious diseases, the benefits resulting from successful application of viral vectors to prevent and treat human diseases can be immense.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhtlWksLrI&md5=b4881747ccbd81ec3110f948216d660b
    69. 69
      Draper, S. J.; Heeney, J. L. Viruses as Vaccine Vectors for Infectious Diseases and Cancer. Nat. Rev. Microbiol. 2010, 8, 62– 73,  DOI: 10.1038/nrmicro2240
      69
      Viruses as vaccine vectors for infectious diseases and cancer
      Draper, Simon J.; Heeney, Jonathan L.
      Nature Reviews Microbiology (2010), 8 (1), 62-73CODEN: NRMACK; ISSN:1740-1526. (Nature Publishing Group)
      A review. Recent developments in the use of viruses as vaccine vectors have been facilitated by a better understanding of viral biol. Advances occur as we gain greater insight into the interrelationship of viruses and the immune system. Viral-vector vaccines remain the best means to induce cellular immunity and are now showing promise for the induction of strong humoral responses. The potential benefits for global health that are offered by this field reflect the scope and utility of viruses as vaccine vectors for human and veterinary applications, with targets ranging from certain types of cancer to a vast array of infectious diseases.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXhsFWksb%252FO&md5=d7d240377ee6d8ca8930b56c292f6aba
    70. 70
      Ura, T.; Okuda, K.; Shimada, M. Developments in Viral Vector-Based Vaccines. Vaccines (Basel, Switz.) 2014, 2, 624– 641,  DOI: 10.3390/vaccines2030624
      70
      Developments in viral vector-based vaccines
      Ura, Takehiro; Okuda, Kenji; Shimada, Masaru
      Vaccines (Basel, Switzerland) (2014), 2 (3), 624-641, 18 pp.CODEN: VBSABP; ISSN:2076-393X. (MDPI AG)
      A review. Viral vectors are promising tools for gene therapy and vaccines. Viral vector-based vaccines can enhance immunogenicity without an adjuvant and induce a robust cytotoxic T lymphocyte (CTL) response to eliminate virus-infected cells. During the last several decades, many types of viruses have been developed as vaccine vectors. Each has unique features and parental virus-related risks. In addn., genetically altered vectors have been developed to improve efficacy and safety, reduce administration dose, and enable large-scale manufg. To date, both successful and unsuccessful results have been reported in clin. trials. These trials provide important information on factors such as toxicity, administration dose tolerated, and optimized vaccination strategy. This review highlights major viral vectors that are the best candidates for clin. use.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXhvFagsr%252FI&md5=2e7a465adbf48ad48378fad19af03842
    71. 71
      Pardi, N.; Tuyishime, S.; Muramatsu, H.; Kariko, K.; Mui, B. L.; Tam, Y. K.; Madden, T. D.; Hope, M. J.; Weissman, D. Expression Kinetics of Nucleoside-Modified MRNA Delivered in Lipid Nanoparticles to Mice by Various Routes. J. Controlled Release 2015, 217, 345– 351,  DOI: 10.1016/j.jconrel.2015.08.007
      71
      Expression kinetics of nucleoside-modified mRNA delivered in lipid nanoparticles to mice by various routes
      Pardi, Norbert; Tuyishime, Steven; Muramatsu, Hiromi; Kariko, Katalin; Mui, Barbara L.; Tam, Ying K.; Madden, Thomas D.; Hope, Michael J.; Weissman, Drew
      Journal of Controlled Release (2015), 217 (), 345-351CODEN: JCREEC; ISSN:0168-3659. (Elsevier B.V.)
      In recent years, in vitro transcribed mRNA (mRNA) has emerged as a potential therapeutic platform. To fulfill its promise, effective delivery of mRNA to specific cell types and tissues needs to be achieved. Lipid nanoparticles (LNPs) are efficient carriers for short-interfering RNAs and have entered clin. trials. However, little is known about the potential of LNPs to deliver mRNA. Here, we generated mRNA-LNPs by incorporating HPLC purified, 1-methylpseudouridine-contg. mRNA comprising codon-optimized firefly luciferase into stable LNPs. Mice were injected with 0.005-0.250 mg/kg doses of mRNA-LNPs by 6 different routes and high levels of protein translation could be measured using in vivo imaging. S.c., i.m. and intradermal injection of the LNP-encapsulated mRNA translated locally at the site of injection for up to 10 days. For several days, high levels of protein prodn. could be achieved in the lung from the intratracheal administration of mRNA. I.v. and i.p. and to a lesser extent i.m. and intratracheal deliveries led to trafficking of mRNA-LNPs systemically resulting in active translation of the mRNA in the liver for 1-4 days. Our results demonstrate that LNPs are appropriate carriers for mRNA in vivo and have the potential to become valuable tools for delivering mRNA encoding therapeutic proteins.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhsV2msr%252FE&md5=35c5150ee9a95ee66bf13786d14b3469
    72. 72
      Dalpke, A. H.; Helm, M. RNA Mediated Toll-Like Receptor Stimulation in Health and Disease. RNA Biol. 2012, 9, 828– 842,  DOI: 10.4161/rna.20206
      72
      RNA mediated toll-like receptor stimulation in health and disease
      Dalpke, Alexander H.; Helm, Mark
      RNA Biology (2012), 9 (6), 828-842CODEN: RBNIBE; ISSN:1547-6286. (Landes Bioscience)
      A review. Besides their well-known functions in storage and translation of information, nucleic acids have emerged as a target of pattern recognition receptors that drive activation of innate immunity. Due to the paucity of building block monomers used in nucleic acids, discrimination of host and microbial nucleic acids as a means of self/foreign discrimination is a complicated task. Pattern recognition receptors rely on discrimination by sequence, structural features and spatial compartmentalization to differentiate microbial derived nucleic acids from host ones. Microbial nucleic acid detection is important for the sensing of infectious danger and initiating an immune response to microbial attack. Failures in the underlying recognitions systems can have severe consequences. Thus, inefficient recognition of microbial nucleic acids may increase susceptibility to infectious diseases. On the other hand, excessive immune responses as a result of failed self/foreign discrimination are assocd. with autoimmune diseases. This review gives a general overview over the underlying concepts of nucleic acid sensing by Toll-like receptors. Within this general framework, we focus on bacterial RNA and synthetic RNA oligomers.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXpsVOhsA%253D%253D&md5=7fb843ce076ecf749cc525cdb6704512
    73. 73
      Heil, F.; Hemmi, H.; Hochrein, H.; Ampenberger, F.; Kirschning, C.; Akira, S.; Lipford, G.; Wagner, H.; Bauer, S. Species-Specific Recognition of Single-Stranded RNA via Toll-Like Receptor 7 and 8. Science 2004, 303, 1526– 1529,  DOI: 10.1126/science.1093620
      73
      Species-Specific Recognition of Single-Stranded RNA via Toll-like Receptor 7 and 8
      Heil, Florian; Hemmi, Hiroaki; Hochrein, Hubertus; Ampenberger, Franziska; Kirschning, Carsten; Akira, Shizuo; Lipford, Grayson; Wagner, Hermann; Bauer, Stefan
      Science (Washington, DC, United States) (2004), 303 (5663), 1526-1529CODEN: SCIEAS; ISSN:0036-8075. (American Association for the Advancement of Science)
      Double-stranded RNA (dsRNA) serves as a danger signal assocd. with viral infection and leads to stimulation of innate immune cells. In contrast, the immunostimulatory potential of single-stranded RNA (ssRNA) is poorly understood and innate immune receptors for ssRNA are unknown. The authors report that guanosine (G)- and uridine (U)-rich ssRNA oligonucleotides derived from human immunodeficiency virus-1 (HIV-1) stimulate dendritic cells (DC) and macrophages to secrete interferon-α and proinflammatory, as well as regulatory, cytokines. By using Toll-like receptor (TLR)-deficient mice and genetic complementation, the authors show that murine TLR7 and human TLR8 mediate species-specific recognition of GU-rich ssRNA. These data suggest that ssRNA represents a physiol. ligand for TLR7 and TLR8.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2cXhslCgsLc%253D&md5=33596446b6a66f5d3f9137eb83aaa242
    74. 74
      Zhang, C.; Maruggi, G.; Shan, H.; Li, J. Advances in MRNA Vaccines for Infectious Diseases. Front. Immunol. 2019, 10, 594,  DOI: 10.3389/fimmu.2019.00594
      74
      Advances in mRNA vaccines for infectious diseases
      Zhang, Cuiling; Maruggi, Giulietta; Shan, Hu; Li, Junwei
      Frontiers in Immunology (2019), 10 (), 594CODEN: FIRMCW; ISSN:1664-3224. (Frontiers Media S.A.)
      A review. During the last two decades, there has been broad interest in RNA-based technologies for the development of prophylactic and therapeutic vaccines. Preclin. and clin. trials have shown that mRNA vaccines provide a safe and long-lasting immune response in animal models and humans. In this , we summarize current research progress on mRNA vaccines, which have the potential to be quick-manufd. and to become powerful tools against infectious disease and we highlight the bright future of their design and applications.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXhtlKhtbjK&md5=687f022a6bad0206ed845775c61f0e39
    75. 75
      Safety and Immunogenicity Study of 2019-nCoV Vaccine (mRNA-1273) for Prophylaxis SARS CoV-2 Infection - Full Text View. ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT04283461 (accessed 2020-04-03).
      There is no corresponding record for this reference.
    76. 76
      Study to Describe the Safety, Tolerability, Immunogenicity, and Potential Efficacy of RNA Vaccine Candidates against COVID-19 in Healthy Adults - Full Text View. ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT04368728 (accessed 2020-05-21).
      There is no corresponding record for this reference.
    77. 77
      A Multi-Site, Phase I/II, 2-Part, Dose-Escalation Trial Investigating the Safety and Immunogenicity of Four Prophylactic SARS-CoV-2 RNA Vaccines against COVID-2019 Using Different Dosing Regimens in Healthy Adults - Full Text View. ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT04380701 (accessed 2020-05-21).
      There is no corresponding record for this reference.
    78. 78
      A Phase I/II Study to Determine Efficacy, Safety and Immunogenicity of the Candidate Coronavirus Disease (COVID-19) Vaccine ChAdOx1 NCoV-19 in UK Healthy Adult Volunteers - Full Text View. ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT04324606 (accessed 2020-05-21).
      There is no corresponding record for this reference.
    79. 79
      Phase I Clinical Trial of a COVID-19 Vaccine in 18–60 Healthy Adults - Full Text View. ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT04313127 (accessed 2020-05-27).
      There is no corresponding record for this reference.
    80. 80
      A Phase II Clinical Trial to Evaluate the Recombinant Vaccine for COVID-19 (Adenovirus Vector) - Full Text View. ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT04341389 (accessed 2020-05-27).
      There is no corresponding record for this reference.
    81. 81
      Safety, Tolerability and Immunogenicity of INO-4800 for COVID-19 in Healthy Volunteers - Full Text View. ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT04336410 (accessed 2020-04-10).
      There is no corresponding record for this reference.
    82. 82
      INOVIO Announces Positive Interim Phase 1 Data For INO-4800 Vaccine for COVID-19. http://ir.inovio.com/news-releases/news-releases-details/2020/INOVIO-Announces-Positive-Interim-Phase-1-Data-For-INO-4800-Vaccine-for-COVID-19/default.aspx (accessed 2020-07-21).
      There is no corresponding record for this reference.
    83. 83
      A Randomized, Double-Blinded, Placebo-Controlled, Phase I/II Clinical Trial, to Evaluate the Safety and Immunogenicity of the SARS-CoV-2 Inactivated Vaccine (Vero Cell) in Healthy Population Aged ≥ 60 Years - Full Text View. ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT04383574 (accessed 2020-05-21).
      There is no corresponding record for this reference.
    84. 84
      Sinovac Reports Positive Data from Phase I/II trials of CoronaVac https://www.clinicaltrialsarena.com/news/sinovac-coronavac-data/ (accessed 2020-08-14).
      There is no corresponding record for this reference.
    85. 85
      China Sinopharm’s Potential COVID-19 Vaccine Triggers Antibodies in Clinical Trials: Journal. Reuters. 2020-08-14.
      There is no corresponding record for this reference.
    86. 86
      Novel Coronavirus (2019-CoV) Inactivated Vaccine (Vero Cell) Phase I/II Clinical Trial. http://www.chictr.org.cn/showproj.aspx?proj=53003 (accessed 2020-08-14).
      There is no corresponding record for this reference.
    87. 87
      http://www.chictr.org.cn/showproj.aspx?proj=53003 (accessed 2020-08-14).
      There is no corresponding record for this reference.
    88. 88
      First COVID-19 Inactivated Vaccine Performs Well in Clinical Trials. http://en.sasac.gov.cn/2020/07/02/c_5178.htm (accessed 2020-08-14).
      There is no corresponding record for this reference.
    89. 89
      An Open Study of the Safety, Tolerability and Immunogenicity of the Drug “Gam-COVID-Vac” Vaccine against COVID-19 - Full Text View. ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT04436471 (accessed 2020-08-03).
      There is no corresponding record for this reference.
    90. 90
      An Open Study of the Safety, Tolerability and Immunogenicity of “Gam-COVID-Vac Lyo” Vaccine against COVID-19 - Full Text View. ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT04437875 (accessed 2020-08-03).
      There is no corresponding record for this reference.
    91. 91
      China’s Zhifei Starts Phase II Trial of COVID-19 Vaccine. Reuters . July 10, 2020. 7 10 DOI: 10.1089/clinomi.07.04.17
      There is no corresponding record for this reference.
    92. 92
      Phase I Clinical Study of Recombinant Novel Coronavirus Vaccine - Full Text View. ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT04445194 (accessed 2020-08-14).
      There is no corresponding record for this reference.
    93. 93
      A 2-Part, Phase 1/2, Randomized, Observer-Blinded Study to Evaluate the Safety and Immunogenicity of a SARS-CoV-2 Recombinant Spike Protein Nanoparticle Vaccine (SARS-CoV-2 RS) with or without MATRIX-MTM Adjuvant in Healthy Subjects - Full Text View. ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT04368988 (accessed 2020-08-14).
      There is no corresponding record for this reference.
    94. 94
      Chowdhury, D. Vaxine Expects to Start Phase II Trials for Potential COVID-19 Vaccine in Weeks. Reuters . July 29, 2020.
      There is no corresponding record for this reference.
    95. 95
      Monovalent Recombinant COVID19 Vaccine - Full Text View. ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT04453852 (accessed 2020-08-14).
      There is no corresponding record for this reference.
    96. 96
      Zydus Cadila’s COVID-19 Vaccine Passes Phase I Safety Trials; Phase II to Test Efficiency Begins 6 August - Health News, Firstpost. https://www.firstpost.com/health/zydus-cadilas-covid-19-vaccine-passes-phase-i-safety-trials-phase-ii-to-test-efficiency-begins-6-august-8674891.html (accessed 2020-08-14).
      There is no corresponding record for this reference.
    97. 97
      Kaur, S. P.; Gupta, V. COVID-19 Vaccine: A Comprehensive Status Report. Virus Res. 2020, 288, 198114,  DOI: 10.1016/j.virusres.2020.198114
      97
      COVID-19 Vaccine: A comprehensive status report
      Kaur, Simran Preet; Gupta, Vandana
      Virus Research (2020), 288 (), 198114CODEN: VIREDF; ISSN:0168-1702. (Elsevier B.V.)
      A review. The current COVID-19 pandemic has urged the scientific community internationally to find answers in terms of therapeutics and vaccines to control SARS-CoV-2. Published investigations mostly on SARS-CoV and to some extent on MERS has taught lessons on vaccination strategies to this novel coronavirus. This is attributed to the fact that SARS-CoV-2 uses the same receptor as SARS-CoV on the host cell i.e. human Angiotensin Converting Enzyme 2 (hACE2) and is approx. 79% similar genetically to SARS-CoV. Though the efforts on COVID-19 vaccines started very early, initially in China, as soon as the outbreak of novel coronavirus erupted and then world-over as the disease was declared a pandemic by WHO. But we will not be having an effective COVID-19 vaccine before Sept., 2020 as per very optimistic ests. This is because a successful COVID-19 vaccine will require a cautious validation of efficacy and adverse reactivity as the target vaccinee population include high-risk individuals over the age of 60, particularly those with chronic co-morbid conditions, frontline healthcare workers and those involved in essentials industries. Various platforms for vaccine development are available namely: virus vectored vaccines, protein subunit vaccines, genetic vaccines, and monoclonal antibodies for passive immunization which are under evaluations for SARS-CoV-2, with each having discrete benefits and hindrances. The COVID-19 pandemic which probably is the most devastating one in the last 100 years after Spanish flu mandates the speedy evaluation of the multiple approaches for competence to elicit protective immunity and safety to curtail unwanted immune-potentiation which plays an important role in the pathogenesis of this virus. This review is aimed at providing an overview of the efforts dedicated to an effective vaccine for this novel coronavirus which has crippled the world in terms of economy, human health and life.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhslejtbfJ&md5=f8319a3df3554fe84038210738752ccf
    98. 98
      COVID-19 Vaccine Reaches Phase-2 Trials in China. http://english.nmpa.gov.cn/2020-06/22/c_502093.htm (accessed 2020-08-14).
      There is no corresponding record for this reference.
    99. 99
      Safety and Immunogenicity Study of an Inactivated SARS-CoV-2 Vaccine for Preventing against COVID-19 in People Aged ⩾60 Years - Full Text View. ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT04470609 (accessed 2020-08-14).
      There is no corresponding record for this reference.
    100. 100
      Richner, J. M.; Himansu, S.; Dowd, K. A.; Butler, S. L.; Salazar, V.; Fox, J. M.; Julander, J. G.; Tang, W. W.; Shresta, S.; Pierson, T. C.; Ciaramella, G.; Diamond, M. S. Modified MRNA Vaccines Protect against Zika Virus Infection. Cell 2017, 168, 1114– 1125,  DOI: 10.1016/j.cell.2017.02.017
      100
      Modified mRNA vaccines protect against Zika virus infection
      Richner, Justin M.; Himansu, Sunny; Dowd, Kimberly A.; Butler, Scott L.; Salazar, Vanessa; Fox, Julie M.; Julander, Justin G.; Tang, William W.; Shresta, Sujan; Pierson, Theodore C.; Ciaramella, Giuseppe; Diamond, Michael S.
      Cell (Cambridge, MA, United States) (2017), 168 (6), 1114-1125.e10CODEN: CELLB5; ISSN:0092-8674. (Cell Press)
      The emergence of ZIKV infection has prompted a global effort to develop safe and effective vaccines. We engineered a lipid nanoparticle (LNP) encapsulated modified mRNA vaccine encoding wild-type or variant ZIKV structural genes and tested immunogenicity and protection in mice. Two doses of modified mRNA LNPs encoding prM-E genes that produced virus-like particles resulted in high neutralizing antibody titers (∼1/100,000) that protected against ZIKV infection and conferred sterilizing immunity. To offset a theor. concern of ZIKV vaccines inducing antibodies that cross-react with the related dengue virus (DENV), we designed modified prM-E RNA encoding mutations destroying the conserved fusion-loop epitope in the E protein. This variant protected against ZIKV and diminished prodn. of antibodies enhancing DENV infection in cells or mice. A modified mRNA vaccine can prevent ZIKV disease and be adapted to reduce the risk of sensitizing individuals to subsequent exposure to DENV, should this become a clin. relevant concern.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXivFensL8%253D&md5=2073ac40e1d084844ae808586333cb29
    101. 101
      Perrie, Y.; Crofts, F.; Devitt, A.; Griffiths, H. R.; Kastner, E.; Nadella, V. Designing Liposomal Adjuvants for the Next Generation of Vaccines. Adv. Drug Delivery Rev. 2016, 99 (Pt A), 85– 96,  DOI: 10.1016/j.addr.2015.11.005
      101
      Designing liposomal adjuvants for the next generation of vaccines
      Perrie, Yvonne; Crofts, Fraser; Devitt, Andrew; Griffiths, Helen R.; Kastner, Elisabeth; Nadella, Vinod
      Advanced Drug Delivery Reviews (2016), 99 (Part_A), 85-96CODEN: ADDREP; ISSN:0169-409X. (Elsevier B.V.)
      Liposomes not only offer the ability to enhance drug delivery, but can effectively act as vaccine delivery systems and adjuvants. Their flexibility in size, charge, bilayer rigidity and compn. allow for targeted antigen delivery via a range of administration routes. In the development of liposomal adjuvants, the type of immune response promoted has been linked to their physico-chem. characteristics, with the size and charge of the liposomal particles impacting on liposome biodistribution, exposure in the lymph nodes and recruitment of the innate immune system. The addn. of immunostimulatory agents can further potentiate their immunogenic properties. Here, we outline the attributes that should be considered in the design and manuf. of liposomal adjuvants for the delivery of sub-unit and nucleic acid based vaccines.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhvVChs7vL&md5=0a957b1de59d473966e0722a1d381203
    102. 102
      Karikó, K.; Muramatsu, H.; Welsh, F. A.; Ludwig, J.; Kato, H.; Akira, S.; Weissman, D. Incorporation of Pseudouridine into MRNA Yields Superior Nonimmunogenic Vector with Increased Translational Capacity and Biological Stability. Mol. Ther. 2008, 16, 1833– 1840,  DOI: 10.1038/mt.2008.200
      102
      Incorporation of pseudouridine into mRNA yields superior nonimmunogenic vector with increased translational capacity and biological stability
      Kariko, Katalin; Muramatsu, Hiromi; Welsh, Frank A.; Ludwig, Janos; Kato, Hiroki; Akira, Shizuo; Weissman, Drew
      Molecular Therapy (2008), 16 (11), 1833-1840CODEN: MTOHCK; ISSN:1525-0016. (Nature Publishing Group)
      In vitro-transcribed mRNAs encoding physiol. important proteins have considerable potential for therapeutic applications. However, in its present form, mRNA is unfeasible for clin. use because of its labile and immunogenic nature. Here, we investigated whether incorporation of naturally modified nucleotides into transcripts would confer enhanced biol. properties to mRNA. We found that mRNAs contg. pseudouridines have a higher translational capacity than unmodified mRNAs when tested in mammalian cells and lysates or administered i.v. into mice at 0.015-0.15 mg/kg doses. The delivered mRNA and the encoded protein could be detected in the spleen at 1, 4, and 24 h after the injection, where both products were at significantly higher levels when pseudouridine-contg. mRNA was administered. Even at higher doses, only the unmodified mRNA was immunogenic, inducing high serum levels of interferon-α (IFN-α). These findings indicate that nucleoside modification is an effective approach to enhance stability and translational capacity of mRNA while diminishing its immunogenicity in vivo. Improved properties conferred by pseudouridine make such mRNA a promising tool for both gene replacement and vaccination.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1cXht12ls7vK&md5=3e575d74308b37b8598a633cd82f3873
    103. 103
      Naylor, R.; Ho, N. W.; Gilham, P. T. Selective Chemical Modifications of Uridine and Pseudouridine in Polynucleotides and Their Effect on the Specificities of Ribonuclease and Phosphodiesterases. J. Am. Chem. Soc. 1965, 87, 4209– 4210,  DOI: 10.1021/ja01096a050
      103
      Selective chemical modifications of uridine and pseudouridine in polynucleotides and their effect on the specificities of ribonuclease and phosphodiesterases
      Naylor, R.; Ho, Nancy W. Y.; Gilham, P. T.
      Journal of the American Chemical Society (1965), 87 (18), 4209-10CODEN: JACSAT; ISSN:0002-7863.
      1-Cyclohexyl-3-(2-morpholinoethyl)carbodiimide metho-p-toluenesulfonate (CMC) added specifically to uridine and guanosine components of RNA such that the modified uridine bases become resistant to the action of pancreatic RNase ( CA 57, 2587d). As a result, digestion of the modified RNA with this enzyme produces oligonucleotides which terminate with cytidine only (CA 63, 833g). When amino acid acceptor RNA from yeast was treated with CMC and hydrolyzed with RNase, no pseudouridine phosphate, uridine phosphate, or corresponding cyclic phosphates were produced. Thus, it appears that pseudouridine is also blocked under the conditions necessary for the blocking of uridine and guanosine. Furthermore, if the modified RNA was treated with dil. NH4OH to remove the blocking groups and then hydrolyzed with RNase, the products obtained were similar to those obtained by the enzymic digestion of untreated RNA except that, in the former case, no pseudouridine phosphate or cyclic phosphate was formed. These results indicate that the pseudouridine bases in RNA form stable adducts with CMC and that the resistance of these adducts to RNase hydrolysis results in the pseudouridine components being left in internal positions of the oligonucleotides that remain after the enzymic digestion. These conclusions were confirmed by a study of the chem. blocking of pseudouridine itself. The rates of hydrolysis of various synthetic dinucleoside phosphates with snake venom and spleen diesterases were tabulated and discussed.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaF2MXkvFSmtLo%253D&md5=379a8ebc183d3b7c20889d37f93dbbab
    104. 104
      Davis, D. R. Stabilization of RNA Stacking by Pseudouridine. Nucleic Acids Res. 1995, 23, 5020– 5026,  DOI: 10.1093/nar/23.24.5020
      104
      Stabilization of RNA stacking by pseudouridine
      Davis, Darrell R.
      Nucleic Acids Research (1995), 23 (24), 5020-6CODEN: NARHAD; ISSN:0305-1048. (Oxford University Press)
      The effect of the modified nucleoside pseudouridine (Ψ) on RNA structure was compared with uridine. The extent of base stacking in model RNA oligonucleotides was measured by 1H NMR, UV, and CD spectroscopy. The UV and CD results indicate that the model single-stranded oligoribonucleotides AAUA and AAΨA from stacked structures in soln. and the CD results for AAΨA are consistent with a general A-form helical conformation. The AAΨA oligomer exhibits a greater degree of UV hypochromicity over the temp. range 5-55°, consistent with a better stacked, more A-form structure compared with AAUA. The extent of stacking for each nucleotide residue was inferred from the percent 3'-endo sugar conformation as indicated by the H1'-H2' NMR scalar coupling. This indirect indication of stacking was confirmed by sequential NOE connectivity patterns obtained from 2D ROESY NMR expts. NMR measurements as a function of temp. indicate that pseudouridine forms a more stable base stacking arrangement than uridine, an effect that is propagated throughout the helix to stabilize stacking of neighboring purine nucleosides. The N1-H imino proton in AAΨA exchanges slowly with solvent, suggesting a role for the extra imino proton in stabilizing the conformation of pseudouridine. These results show that the conformational stabilization is an intrinsic property of pseudouridine occurring at the nucleotide level. The characteristics of pseudouridine in these models are consistent with earlier studies on intact tRNA, indicating that pseudouridine probably performs the same stabilizing function in most structural contexts.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK28XlsVCktg%253D%253D&md5=b1284db31e2266ee1593e3b377ec79a5
    105. 105
      Tai, W.; Zhao, G.; Sun, S.; Guo, Y.; Wang, Y.; Tao, X.; Tseng, C.-T. K.; Li, F.; Jiang, S.; Du, L.; Zhou, Y. A Recombinant Receptor-Binding Domain of MERS-CoV in Trimeric Form Protects Human Dipeptidyl Peptidase 4 (HDPP4) Transgenic Mice from MERS-CoV Infection. Virology 2016, 499, 375– 382,  DOI: 10.1016/j.virol.2016.10.005
      105
      A recombinant receptor-binding domain of MERS-CoV in trimeric form protects human dipeptidyl peptidase 4 (hDPP4) transgenic mice from MERS-CoV infection
      Tai, Wanbo; Zhao, Guangyu; Sun, Shihun; Guo, Yan; Wang, Yufei; Tao, Xinrong; Tseng, Chien-Te K.; Li, Fang; Jiang, Shibo; Du, Lanying; Zhou, Yusen
      Virology (2016), 499 (), 375-382CODEN: VIRLAX; ISSN:0042-6822. (Elsevier B.V.)
      Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV) was first identified in 2012, and it continues to threaten human health worldwide. No MERS vaccines are licensed for human use, reinforcing the urgency to develop safe and efficacious vaccines to prevent MERS. MERS-CoV spike protein forms a trimer, and its receptor-binding domain (RBD) serves as a vaccine target. Nevertheless, the protective efficacy of RBD in its native trimeric form has never been evaluated. In this study, a trimeric protein, RBD-Fd, was generated by fusing RBD with foldon trimerization motif. It bound strongly to the receptor of MERS-CoV, dipeptidyl peptidase 4 (DPP4), and elicited robust RBD-specific neutralizing antibodies in mice, maintaining long-term neutralizing activity against MERS-CoV infection. RBD-Fd potently protected hDPP4 transgenic mice from lethal MERS-CoV challenge. These results suggest that MERS-CoV RBD in its trimeric form maintains native conformation and induces protective neutralizing antibodies, making it a candidate for further therapeutic development.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28Xhs1yqsbzM&md5=c372450b91d5d39330143c81166f764e
    106. 106
      A Study to Evaluate Efficacy, Safety, and Immunogenicity of mRNA-1273 Vaccine in Adults Aged 18 Years and Older to Prevent COVID-19 - Full Text View. ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT04470427 (accessed 2020-08-10).
      There is no corresponding record for this reference.
    107. 107
      Study to Describe the Safety, Tolerability, Immunogenicity, and Efficacy of RNA Vaccine Candidates against COVID-19 in Healthy Adults - Full Text View. ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT04368728 (accessed 2020-08-03).
      There is no corresponding record for this reference.
    108. 108
      INO-4800 DNA Coronavirus Vaccine https://www.precisionvaccinations.com/vaccines/ino-4800-dna-coronavirus-vaccine (accessed 2020-08-14).
      There is no corresponding record for this reference.
    109. 109
      Cohen, J. with Record-Setting Speed, Vaccinemakers Take Their First Shots at the New Coronavirus. https://www.sciencemag.org/news/2020/03/record-setting-speed-vaccine-makers-take-their-first-shots-new-coronavirus (accessed 2020-08-14).
      There is no corresponding record for this reference.
    110. 110
      Lowe, D. The Russian Vaccine. https://blogs.sciencemag.org/pipeline/archives/2020/08/11/the-russian-vaccine (accessed 2020-08-14).
      There is no corresponding record for this reference.
    111. 111
      Skepticism Greets Putin’s Announcement Of Russian Coronavirus Vaccine. https://www.npr.org/sections/coronavirus-live-updates/2020/08/11/901270401/skepticism-greets-putins-announcement-of-russian-coronavirus-vaccine (accessed 2020-08-14).
      There is no corresponding record for this reference.
    112. 112
      Closing in on a COVID-19 Vaccine. https://www.eurekalert.org/pub_releases/2020-04/fu-cio040220.php (accessed 2020-04-19).
      There is no corresponding record for this reference.
    113. 113
      Dicks, M. D. J.; Spencer, A. J.; Edwards, N. J.; Wadell, G.; Bojang, K.; Gilbert, S. C.; Hill, A. V. S.; Cottingham, M. G. A Novel Chimpanzee Adenovirus Vector with Low Human Seroprevalence: Improved Systems for Vector Derivation and Comparative Immunogenicity. PLoS One 2012, 7, e40385  DOI: 10.1371/journal.pone.0040385
      113
      A novel chimpanzee adenovirus vector with low human seroprevalence: improved systems for vector derivation and comparative immunogenicity
      Dicks, Matthew D. J.; Spencer, Alexandra J.; Edwards, Nick J.; Wadell, Goeran; Bojang, Kalifa; Gilbert, Sarah C.; Hill, Adrian V. S.; Cottingham, Matthew G.
      PLoS One (2012), 7 (7), e40385CODEN: POLNCL; ISSN:1932-6203. (Public Library of Science)
      Recombinant adenoviruses are among the most promising tools for vaccine antigen delivery. Recently, the development of new vectors has focused on serotypes to which the human population is less exposed in order to circumvent pre-existing anti vector immunity. This study describes the derivation of a new vaccine vector based on a chimpanzee adenovirus, Y25, together with a comparative assessment of its potential to elicit transgene product specific immune responses in mice. The vector was constructed in a bacterial artificial chromosome to facilitate genetic manipulation of genomic clones. In order to conduct a fair head-to-head immunol. comparison of multiple adenoviral vectors, we optimized a method for accurate detn. of infectious titer, since this parameter exhibits profound natural variability and can confound immunogenicity studies when doses are based on viral particle estn. Cellular immunogenicity of recombinant E1 E3-deleted vector ChAdY25 was comparable to that of other species E derived chimpanzee adenovirus vectors including ChAd63, the first simian adenovirus vector to enter clin. trials in humans. Furthermore, the prevalence of virus neutralizing antibodies (titer >1:200) against ChAdY25 in serum samples collected from two human populations in the UK and Gambia was particularly low compared to published data for other chimpanzee adenoviruses. These findings support the continued development of new chimpanzee adenovirus vectors, including ChAdY25, for clin. use.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhtVyisrvN&md5=dc7f267cde7ad2f6916097d25923a9fc
    114. 114
      Li, L.; Petrovsky, N. Molecular Mechanisms for Enhanced DNA Vaccine Immunogenicity. Expert Rev. Vaccines 2016, 15, 313– 329,  DOI: 10.1586/14760584.2016.1124762
      114
      Molecular mechanisms for enhanced DNA vaccine immunogenicity
      Li, Lei; Petrovsky, Nikolai
      Expert Review of Vaccines (2016), 15 (3), 313-329CODEN: ERVXAX; ISSN:1476-0584. (Taylor & Francis Ltd.)
      In the two decades since their initial discovery, DNA vaccines technologies have come a long way. Unfortunately, when applied to human subjects inadequate immunogenicity is still the biggest challenge for practical DNA vaccine use. Many different strategies have been tested in preclin. models to address this problem, including novel plasmid vectors and codon optimization to enhance antigen expression, new gene transfection systems or electroporation to increase delivery efficiency, protein or live virus vector boosting regimens to maximise immune stimulation, and formulation of DNA vaccines with traditional or mol. adjuvants. Better understanding of the mechanisms of action of DNA vaccines has also enabled better use of the intrinsic host response to DNA to improve vaccine immunogenicity. This review summarizes recent advances in DNA vaccine technologies and related intracellular events and how these might impact on future directions of DNA vaccine development.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXitV2msbnJ&md5=fabe70b4f42c741d0fc1086b6e6abc84
    115. 115
      Coughlan, L. Factors Which Contribute to the Immunogenicity of Non-Replicating Adenoviral Vectored Vaccines. Front. Immunol. 2020, 11. DOI: 10.3389/fimmu.2020.00909
      There is no corresponding record for this reference.
    116. 116
      CanSino to Conduct Phase III Covid-19 Vaccine Trial in Saudi Arabia. https://www.clinicaltrialsarena.com/news/cansino-vaccine-saudi-trial/ (accessed 2020-08-10).
      There is no corresponding record for this reference.
    117. 117
      A Phase III Study to Investigate a Vaccine against COVID-19. http://www.isrctn.com/ISRCTN89951424 (accessed 2020-08-10).
      There is no corresponding record for this reference.
    118. 118
      Ella, K. M.; Mohan, V. K. Coronavirus Vaccine: Light at the End of the Tunnel. Indian Pediatr. 2020, 57, 407– 410,  DOI: 10.1007/s13312-020-1812-z
      118
      Coronavirus Vaccine: Light at the End of the Tunnel
      Ella Krishna M; Mohan V Krishna
      Indian pediatrics (2020), 57 (5), 407-410 ISSN:.
      The world is currently facing an unprecedented global pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Predicting the next source of the pandemic can be very challenging. As vaccination is the best way to prevent an infectious disease, the development of an effective vaccine against SARS-CoV-2 can not only reduce the morbidity and mortality associated with it, but can also lessen the economic impact. As the traditional method of vaccine development takes many years for a vaccine to be available to the society, the vaccine development for SARS-CoV-2 should be speeded up using a pandemic approach with fast-track approvals from the regulatory authorities. Various challenges associated with developing a vaccine during the pandemic such as technological hurdles, clinical development pathways, regulatory issues, and support from global funding agencies are expressed here.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB38zltlaqtQ%253D%253D&md5=a267cd0fd76ae1849d65f711902e2210
    119. 119
      Genexine, Y Biologics to Co-Develop Covid-19 Treatment - Korea Biomedical Review. http://www.koreabiomed.com/news/articleView.html?idxno=8800 (accessed 2020-08-03).
      There is no corresponding record for this reference.
    120. 120
      Japan’s AnGes Speeds Toward 2021 Rollout in Coronavirus “Vaccine War. https://www.japantimes.co.jp/news/2020/06/11/national/science-health/anges-coronavirus-vaccine-war/ (accessed 2020-08-03).
      There is no corresponding record for this reference.
    121. 121
      Weiner, D. B. RNA-Based Vaccination: Sending a Strong Message. Mol. Ther. 2013, 21, 506– 508,  DOI: 10.1038/mt.2013.26
      121
      RNA-Based Vaccination: Sending a Strong Message
      Weiner, David B.
      Molecular Therapy (2013), 21 (3), 506-508CODEN: MTOHCK; ISSN:1525-0016. (Nature Publishing Group)
      A review. This commentary reports on nucleic acid-based vaccines (NAVs) for induction of antigen-specific immunity and their emergence as important tools in our vaccine/immune therapeutic arsenal.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXjtlaksb0%253D&md5=e335f7c4d635d8f7952945de9b88cff2
    122. 122
      Watanabe, Y.; Allen, J. D.; Wrapp, D.; McLellan, J. S.; Crispin, M. Site-Specific Glycan Analysis of the SARS-CoV-2 Spike. Science 2020, 369, 330– 333,  DOI: 10.1126/science.abb9983
      122
      Site-specific glycan analysis of the SARS-CoV-2 spike
      Watanabe, Yasunori; Allen, Joel D.; Wrapp, Daniel; McLellan, Jason S.; Crispin, Max
      Science (Washington, DC, United States) (2020), 369 (6501), 330-333CODEN: SCIEAS; ISSN:1095-9203. (American Association for the Advancement of Science)
      The emergence of the betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), represents a considerable threat to global human health. Vaccine development is focused on the principal target of the humoral immune response, the spike (S) glycoprotein, which mediates cell entry and membrane fusion. The SARS-CoV-2 S gene encodes 22 N-linked glycan sequons per protomer, which likely play a role in protein folding and immune evasion. Here, using a site-specific mass spectrometric approach, we reveal the glycan structures on a recombinant SARS-CoV-2 S immunogen. This anal. enables mapping of the glycan-processing states across the trimeric viral spike. We show how SARS-CoV-2 S glycans differ from typical host glycan processing, which may have implications in viral pathobiol. and vaccine design.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXhsVSjtLnE&md5=e751e60b601f2c20ff3f1b1d0ef45a3f
    123. 123
      Khan, K. H. DNA Vaccines: Roles against Diseases. GERMS 2013, 3, 26– 35,  DOI: 10.11599/germs.2013.1034
      123
      DNA vaccines: roles against diseases
      Khan, Kishwar Hayat
      GERMS (2013), 3 (1), 26-35CODEN: GERMCF; ISSN:2248-2997. (European Academy of HIV/AIDS and Infectious Diseases)
      A review. Vaccination is the most successful application of immunol. principles to human health. Vaccine efficacy needs to be reviewed from time to time and its safety is an overriding consideration. DNA vaccines offer simple yet effective means of inducing broad-based immunity. These vaccines work by allowing the expression of the microbial antigen inside host cells that take up the plasmid. These vaccines function by generating the desired antigen inside the cells, with the advantage that this may facilitate presentation through the major histocompatibility complex. This review article is based on a literature survey and it describes the working and designing strategies of DNA vaccines. Advantages and disadvantages for this type of vaccines have also been explained, together with applications of DNA vaccines. DNA vaccines against cancer, tuberculosis, Edwardsiella tarda, HIV, anthrax, influenza, malaria, dengue, typhoid and other diseases were explored.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXnsVCht7o%253D&md5=a3c61bd65fa88affbda37334047465e0
    124. 124
      Alarcon, J. B.; Waine, G. W.; McManus, D. P. DNA Vaccines: Technology and Application as Anti-Parasite and Anti-Microbial Agents. Adv. Parasitol. 1999, 42, 343– 410,  DOI: 10.1016/S0065-308X(08)60152-9
      124
      DNA vaccines: technology and application as anti-parasite and anti-microbial agents
      Alarcon J B; Waine G W; McManus D P
      Advances in parasitology (1999), 42 (), 343-410 ISSN:0065-308X.
      DNA vaccines have been termed The Third Generation of Vaccines. The recent successful immunization of experimental animals against a range of infectious agents and several tumour models of disease with plasmid DNA testifies to the powerful nature of this revolutionary approach in vaccinology. Among numerous advantages, a major attraction of DNA vaccines over conventional vaccines is that they are able to induce protective cytotoxic T-cell responses as well as helper T-cell and humoral immunity. Here we review the current state of nucleic acid vaccines and cover a wide range of topics including delivery mechanisms, uptake and expression of plasmid DNA, and the types of immune responses generated. Further, we discuss safety issues, and document the use of nucleic acid vaccines against viral, bacterial and parasitic diseases, and cancer. The early potential promise of DNA vaccination has been fully substantiated with recent, exciting developments including the movement from testing DNA vaccines in laboratory models to non-human primates and initial human clinical trials. These advances and the emerging voluminous literature on DNA vaccines highlight the rapid progress that has been made in the DNA immunization field. It will be of considerable interest to see whether the progress and optimism currently prevailing can be maintained, and whether the approach can indeed fulfil the medical and commerical promise anticipated.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADyaK1M7lvFWrsQ%253D%253D&md5=3be15a1d0595e7d6b099df240e595c5e
    125. 125
      Geall, A. J.; Verma, A.; Otten, G. R.; Shaw, C. A.; Hekele, A.; Banerjee, K.; Cu, Y.; Beard, C. W.; Brito, L. A.; Krucker, T.; O’Hagan, D. T.; Singh, M.; Mason, P. W.; Valiante, N. M.; Dormitzer, P. R.; Barnett, S. W.; Rappuoli, R.; Ulmer, J. B.; Mandl, C. W. Nonviral Delivery of Self-Amplifying RNA Vaccines. Proc. Natl. Acad. Sci. U. S. A. 2012, 109, 14604– 14609,  DOI: 10.1073/pnas.1209367109
      125
      Nonviral delivery of self-amplifying RNA vaccines
      Geall, Andrew J.; Verma, Ayush; Otten, Gillis R.; Shaw, Christine A.; Hekele, Armin; Banerjee, Kaustuv; Cu, Yen; Beard, Clayton W.; Brito, Luis A.; Krucker, Thomas; O'Hagan, Derek T.; Singh, Manmohan; Mason, Peter W.; Valiante, Nicholas M.; Dormitzer, Philip R.; Barnett, Susan W.; Rappuoli, Rino; Ulmer, Jeffrey B.; Mandl, Christian W.
      Proceedings of the National Academy of Sciences of the United States of America (2012), 109 (36), 14604-14609, S14604/1-S14604/7CODEN: PNASA6; ISSN:0027-8424. (National Academy of Sciences)
      Despite more than two decades of research and development on nucleic acid vaccines, there is still no com. product for human use. Taking advantage of the recent innovations in systemic delivery of short interfering RNA (siRNA) using lipid nanoparticles (LNPs), we developed a self-amplifying RNA vaccine. Here we show that nonviral delivery of a 9-kb self-amplifying RNA encapsulated within an LNP substantially increased immunogenicity compared with delivery of unformulated RNA. This unique vaccine technol. was found to elicit broad, potent, and protective immune responses, that were comparable to a viral delivery technol., but without the inherent limitations of viral vectors. Given the many pos. attributes of nucleic acid vaccines, our results suggest that a comprehensive evaluation of nonviral technologies to deliver self-amplifying RNA vaccines is warranted.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhsVaqu7zI&md5=2a9e33500776ed4b5db9c1dd4a3ab183
    126. 126
      Kirkpatrick, D. D. U.K. Lab to Sidestep Drug Industry to Sell Potential Virus Vaccine. New York Times Jun 7, 2020.
      There is no corresponding record for this reference.
    127. 127
      Petsch, B.; Schnee, M.; Vogel, A. B.; Lange, E.; Hoffmann, B.; Voss, D.; Schlake, T.; Thess, A.; Kallen, K.-J.; Stitz, L.; Kramps, T. Protective Efficacy of in Vitro Synthesized, Specific MRNA Vaccines against Influenza A Virus Infection. Nat. Biotechnol. 2012, 30, 1210– 1216,  DOI: 10.1038/nbt.2436
      127
      Protective efficacy of in vitro synthesized, specific mRNA vaccines against influenza A virus infection
      Petsch, Benjamin; Schnee, Margit; Vogel, Annette B.; Lange, Elke; Hoffmann, Bernd; Voss, Daniel; Schlake, Thomas; Thess, Andreas; Kallen, Karl-Josef; Stitz, Lothar; Kramps, Thomas
      Nature Biotechnology (2012), 30 (12), 1210-1216CODEN: NABIF9; ISSN:1087-0156. (Nature Publishing Group)
      Despite substantial improvements, influenza vaccine prodn.-and availability-remain suboptimal. Influenza vaccines based on mRNA may offer a soln. as sequence-matched, clin.-grade material could be produced reliably and rapidly in a scalable process, allowing quick response to the emergence of pandemic strains. Here we show that mRNA vaccines induce balanced, long-lived and protective immunity to influenza A virus infections in even very young and very old mice and that the vaccine remains protective upon thermal stress. This vaccine format elicits B and T cell-dependent protection and targets multiple antigens, including the highly conserved viral nucleoprotein, indicating its usefulness as a cross-protective vaccine. In ferrets and pigs, mRNA vaccines induce immunol. correlates of protection and protective effects similar to those of a licensed influenza vaccine in pigs. Thus, mRNA vaccines could address substantial medical need in the area of influenza prophylaxis and the broader realm of anti-infective vaccinol.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38Xhs1ymsbjO&md5=11dd1307065ed07df9ea1f009d7d484c
    128. 128
      Fotin-Mleczek, M.; Duchardt, K. M.; Lorenz, C.; Pfeiffer, R.; Ojkic-Zrna, S.; Probst, J.; Kallen, K.-J. Messenger RNA-Based Vaccines With Dual Activity Induce Balanced TLR-7 Dependent Adaptive Immune Responses and Provide Antitumor Activity. J. Immunother. 2011, 34, 1– 15,  DOI: 10.1097/CJI.0b013e3181f7dbe8
      128
      Messenger RNA-based vaccines with dual activity induce balanced TLR-7 dependent adaptive immune responses and provide antitumor activity
      Fotin-Mleczek Mariola; Duchardt Katharina M; Lorenz Christina; Pfeiffer Regina; Ojkic-Zrna Sanja; Probst Jochen; Kallen Karl-Josef
      Journal of immunotherapy (Hagerstown, Md. : 1997) (2011), 34 (1), 1-15 ISSN:.
      Direct vaccination with messenger RNA (mRNA) molecules encoding tumor-associated antigens is a novel and promising approach in cancer immunotherapy. The main advantage of using mRNA for vaccination is that the same molecule not only provides an antigen source for adaptive immunity, but can simultaneously bind to pattern recognition receptors, thus stimulating innate immunity. However, achieving both features remains challenging, as the complexation of mRNA required for immune-stimulating activity may inhibit its translatability. In this study, we present a new and more effective vaccine design: a two-component mRNA-based tumor vaccine that supports both: antigen expression and immune stimulation, mediated by Toll like receptor 7 (TLR7). The two-component mRNA vaccines, containing free and protamine-complexed mRNA, induce balanced adaptive immune responses providing humoral as well as T cell mediated immunity. This balanced immune response is based on the induction of antigen-specific CD4(+) T helper cells and cytotoxic CD8(+) T cells. Once activated, these CD4(+) and CD8(+) T cells secrete a wide set of cytokines, which drive a TH1 response. Immunization with the two-component vaccines induces sustained memory responses, mediated by antigen-specific memory T cells. Moreover, treatment of mice with the two-component mRNA vaccine mediates a strong antitumor response against OVA-expressing tumor cells, not only in a prophylactic but also in a therapeutic setting. In conclusion, two-component mRNA vaccines with self-adjuvanting activity induce balanced adaptive immune responses and mediate sustained antitumor activity.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC3M%252FktFGntA%253D%253D&md5=8fea4b31d8126e34caeb4c30a3e91ce0
    129. 129
      Bangari, D. S.; Mittal, S. K. Development of Nonhuman Adenoviruses as Vaccine Vectors. Vaccine 2006, 24, 849– 862,  DOI: 10.1016/j.vaccine.2005.08.101
      129
      Development of nonhuman adenoviruses as vaccine vectors
      Bangari, Dinesh S.; Mittal, Suresh K.
      Vaccine (2006), 24 (7), 849-862CODEN: VACCDE; ISSN:0264-410X. (Elsevier B.V.)
      A review. Human adenoviral (HAd) vectors have demonstrated great potential as vaccine vectors. Preclin. and clin. studies have demonstrated the feasibility of vector design, robust antigen expression and protective immunity using this system. However, clin. use of adenoviral vectors for vaccine purposes is anticipated to be limited by vector immunity that is either preexisting or develops rapidly following the first inoculation with adenoviral vectors. Vector immunity inactivates the vector particles and rapidly removes the transduced cells, thereby limiting the duration of transgene expression. Due to strong vector immunity, subsequent use of the same vector is usually less efficient. In order to circumvent this limitation, nonhuman adenoviral vectors have been proposed as alternative vectors. In addn. to eluding HAd immunity, these vectors possess most of the attractive features of HAd vectors. Several replication-competent or replication-defective nonhuman adenoviral vectors have been developed and investigated for their potential as vaccine-delivery vectors. Here, we review recent advances in the design and characterization of various nonhuman adenoviral vectors, and discuss their potential applications for human and animal vaccination.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD28Xhtleit7k%253D&md5=7d3e1591d789b682fe413269adad4b38
    130. 130
      Crawford-Miksza, L.; Schnurr, D. P. Analysis of 15 Adenovirus Hexon Proteins Reveals the Location and Structure of Seven Hypervariable Regions Containing Serotype-Specific Residues. J. Virol. 1996, 70, 1836– 1844,  DOI: 10.1128/JVI.70.3.1836-1844.1996
      130
      Analysis of 15 adenovirus hexon proteins reveals the location and structure of seven hypervariable regions containing serotype-specific residues
      Crawford-Miksza, Leta; Schnurr, David P.
      Journal of Virology (1996), 70 (3), 1836-44CODEN: JOVIAM; ISSN:0022-538X. (American Society for Microbiology)
      The first full-length hexon protein DNA and deduced amino acid sequences of a subgenus D adenovirus (AV) were detd. from candidate AV48 (85-0844). Comprehensive comparison of this sequence with hexon protein sequences from human subgenera A, B, C, D, F, bovine AV3, and mouse AV1 revealed seven discrete hypervariable regions (HVRs) among the 250 variable residues in loops 1 and 2. These regions differed in length between serotypes, from 2 to 38 residues, and contained >99% of hexon serotype-specific residues among human serotypes. Alignment with the published crystal structure of AV2 established the location and structure of the type-specific regions. Five HVRs were shown to be part of linear loops on the exposed surfaces of the protein, analogous to the serotype-specific loops or "puffs" in picornavirus capsid proteins. The HVRs were supported by a common framework of conserved residues, of which 68 to 75% were hydrophobic. Unique sequences were limited to the seven HVRs, so that one or more of these regions contain the type-specific neutralization epitopes. A neutralizing AV48 hexon-specific antiserum recognized linear peptides that corresponded to six HVRs by enzyme immunoassay. Affinity-purifn. removal of all peptide-reactive antibodies did not significantly decrease the neutralization titer. Eluted peptide-reactive antibodies did not neutralize. Human antisera that neutralized AV48 did not recognize linear peptides. Purified trimeric native hexon inhibited neutralization, but monomeric heat-denatured hexon did not. We conclude that the AV48 neutralization epitope(s) is complex and conformational.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK28XpvFaktg%253D%253D&md5=e5cb61f4a392ec45b3f42f5a1801206b
    131. 131
      Baxi, M. K.; Deregt, D.; Robertson, J.; Babiuk, L. A.; Schlapp, T.; Tikoo, S. K. Recombinant Bovine Adenovirus Type 3 Expressing Bovine Viral Diarrhea Virus Glycoprotein E2 Induces an Immune Response in Cotton Rats. Virology 2000, 278, 234– 243,  DOI: 10.1006/viro.2000.0661
      131
      Recombinant Bovine Adenovirus Type 3 Expressing Bovine Viral Diarrhea Virus Glycoprotein E2 Induces an Immune Response in Cotton Rats
      Baxi, Mohit K.; Deregt, Dirk; Robertson, Jill; Babiuk, Lorne A.; Schlapp, Tobias; Tikoo, Suresh K.
      Virology (2000), 278 (1), 234-243CODEN: VIRLAX; ISSN:0042-6822. (Academic Press)
      Recombinant bovine adenovirus is being developed as a live vector for animal vaccination and for human gene therapy. In this study, two replication-competent bovine adenovirus 3 (BAV-3) recombinants (BAV331 and BAV338) expressing bovine viral diarrhea virus (BVDV) glycoprotein E2 in the early region 3 (E3) of BAV-3 were constructed. Recombinant BAV331 contains chem. synthesized E2 gene (nucleotides modified to remove internal cryptic splice sites) under the control of BAV-3 E3/major late promoter (MLP), while recombinant BAV338 contains original E2 gene under the control of human cytomegalovirus immediate early promoter. Since E2, a class I membrane glycoprotein, does not contain its own signal peptide sequence at the 5' end, the bovine herpesvirus 1 (BHV-1) glycoprotein D signal sequence was fused in frame to the E2 open reading frame (ORF) for proper processing of the E2 glycoprotein in both the recombinant viruses. Recombinant E2 protein expressed by BAV331 and BAV338 recombinant viruses was recognized by E2-specific monoclonal antibodies as a 53-kDa protein, which also formed dimer with an apparent mol. wt. of 94 kDa. Insertion of an E2-expression cassette in the E3 region did not effect the replication of recombinant BAV-3s. Intranasal immunization of cotton rats with these recombinant viruses generated E2-specific IgA and IgG responses at the mucosal surfaces and in the serum. In summary, these results show that the pestivirus glycoprotein can be expressed efficiently by BAV-3. In addn., mucosal immunization with replication-competent recombinant bovine adenovirus 3 can induce a specific immune response against the expressed antigen. (c) 2000 Academic Press.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3cXosFGns7s%253D&md5=b0a98f1199b3c9543b873b40a4ccb10c
    132. 132
      Fischer, L.; Tronel, J. P.; Pardo-David, C.; Tanner, P.; Colombet, G.; Minke, J.; Audonnet, J.-C. Vaccination of Puppies Born to Immune Dams with a Canine Adenovirus-Based Vaccine Protects against a Canine Distemper Virus Challenge. Vaccine 2002, 20, 3485– 3497,  DOI: 10.1016/S0264-410X(02)00344-4
      132
      Vaccination of puppies born to immune dams with a canine adenovirus-based vaccine protects against a canine distemper virus challenge
      Fischer, Laurent; Tronel, Jean Philippe; Pardo-David, Camilla; Tanner, Patrick; Colombet, Guy; Minke, Jules; Audonnet, Jean-Christophe
      Vaccine (2002), 20 (29-30), 3485-3497CODEN: VACCDE; ISSN:0264-410X. (Elsevier Science Ltd.)
      None of the currently available distemper vaccines provides a satisfactory soln. for the immunization of very young carnivores in the face of maternal-derived immunity. Since mucosal immunization with replication-competent adenovirus-based vaccines has been proven effective in the face of passive immunity against the vector, it has the potential to provide a soln. for the vaccination of young puppies born to canine distemper virus (CDV)-immune dams. The authors report the engineering and the characterization of two replication-competent canine adenovirus type 2 (CAV2)-based vaccines expressing, resp., the CDV hemagglutinin (HA) and fusion (F) antigens. The authors first demonstrated that the intranasal vaccination with a mixt. of both recombinant CAV2s provides an excellent level of protection in seroneg. puppies, confirming the value of replication-competent adenovirus-based vectors for mucosal vaccination. In contrast, intranasal immunization with the same vaccine of puppies born to CDV- and CAV2-immune dams, failed to activate specific and protective immune responses. The authors hypothesized that an active CAV2 infection occurred while puppies were in close contact with the vaccinated dams in the breeding units and that the resulting active mucosal immunity interfered with the intranasal administration of CAV2-based CDV vaccine. However, when puppies born to CDV- and CAV2-immune dams were vaccinated s.c. with the CAV2-based CDV vaccine, significant seroconversion and solid protective immunity were triggered despite pre-existing systemic immunity to the vector. This latter result is surprising and suggests that s.c. vaccination with a replication-competent recombinant CAV2 may be an efficient strategy to overcome both passive and active adenovirus specific immunity in the dog. From a practical point of view, this could pave the way for an original strategy to vaccinate young puppies in the face of maternal-derived immunity.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD38Xnt1Crurg%253D&md5=07512a3d42f159ecb3c73e3e57c4b795
    133. 133
      Wüest, T.; Both, G. W.; Prince, A. M.; Hofmann, C.; Löser, P. Recombinant Ovine Atadenovirus Induces a Strong and Sustained T Cell Response against the Hepatitis C Virus NS3 Antigen in Mice. Vaccine 2004, 22, 2717– 2721,  DOI: 10.1016/j.vaccine.2004.01.048
      There is no corresponding record for this reference.
    134. 134
      Bangari, D. S.; Mittal, S. K. Porcine Adenoviral Vectors Evade Preexisting Humoral Immunity to Adenoviruses and Efficiently Infect Both Human and Murine Cells in Culture. Virus Res. 2004, 105, 127– 136,  DOI: 10.1016/j.virusres.2004.05.003
      134
      Porcine adenoviral vectors evade preexisting humoral immunity to adenoviruses and efficiently infect both human and murine cells in culture
      Bangari, Dinesh S.; Mittal, Suresh K.
      Virus Research (2004), 105 (2), 127-136CODEN: VIREDF; ISSN:0168-1702. (Elsevier B.V.)
      Preexisting immunity against human adenoviruses (HAd) limits the efficiency of transduction of HAd vectors in humans. In addn., development of a vector-specific immune response after the first inoculation with a HAd vector further lowers vector uptake following readministration. The authors investigated the usefulness of porcine adenovirus serotype 3 (PAd3)-based vectors as a supplement to HAd vectors. Here the authors demonstrate that preexisting HAd-specific neutralizing antibodies in humans do not cross-neutralize PAd3. To generate E1A-deleted PAd3 vectors, an E1-complementing cell line of porcine origin was produced. E1A-deleted PAd3 vector expressing green fluorescent protein; GFP (PAd-GFP) and E1-deleted HAd5 vector expressing GFP (HAd-GFP) transduced human cell lines with comparable efficiencies. Both of these vectors efficiently transduced murine MT1A2 breast cancer cell line, while PAd-GFP transduced murine NIH 3T3 fibroblast cell line significantly better than HAd-GFP. These results suggest that PAd3 vectors would be promising supplement to HAd vectors as a delivery vehicle for recombinant vaccines and gene therapy applications.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2cXntlSmtLs%253D&md5=7d8313d9cdb45ba7ea86d191d4479ec7
    135. 135
      Rasmussen, U. B.; Benchaibi, M.; Meyer, V.; Schlesinger, Y.; Schughart, K. Novel Human Gene Transfer Vectors: Evaluation of Wild-Type and Recombinant Animal Adenoviruses in Human-Derived Cells. Hum. Gene Ther. 1999, 10, 2587– 2599,  DOI: 10.1089/10430349950016636
      135
      Novel human gene transfer vectors: evaluation of wild-type and recombinant animal adenoviruses in human-derived cells
      Rasmussen, Ulla B.; Benchaibi, Miloud; Meyer, Veronique; Schlesinger, Yasmin; Schughart, Klaus
      Human Gene Therapy (1999), 10 (16), 2587-2599CODEN: HGTHE3; ISSN:1043-0342. (Mary Ann Liebert, Inc.)
      Major disadvantages of human adenovirus (hAd) vectors in gene therapy include preexisting or induced immune responses, and possible coreplication of recombinant hAd in the presence of wild-type hAds. These disadvantages may be overcome by using nonhuman, animal adenoviruses (aAds). We evaluated four different aAds for their potential use as viral vectors. The canine adenovirus type 2 (CAV2) and bovine adenovirus type 3 (BAV3) appeared to be suitable systems, as they infect human cells. CAV2, but not BAV3, caused cytotoxicity, and only limited (CAV2) or no (BAV3) prodn. of infectious virus particles was obsd. after infection of human cell lines. CAV2 showed higher expression of endogenous genes than did BAV3 in the tested human cells. No interference between hAd and CAV2 or BAV3, such as recombination of DNA or cross-activation of virus replication, was obsd. in up to five passages in double-infected human cells. Transfection of cloned genomic CAV2 or BAV3 DNA into appropriate permissive cell lines rescued infectious virus. Furthermore, we produced a recombinant E1-deleted BAV3, and showed that it could infect and express a reporter gene in various human cell types.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK1MXnt1yrsL8%253D&md5=97881cc59c410700f3dd866f158ffbff
    136. 136
      Bangari, D. S.; Shukla, S.; Mittal, S. K. Comparative Transduction Efficiencies of Human and Nonhuman Adenoviral Vectors in Human, Murine, Bovine, and Porcine Cells in Culture. Biochem. Biophys. Res. Commun. 2005, 327, 960– 966,  DOI: 10.1016/j.bbrc.2004.12.099
      136
      Comparative transduction efficiencies of human and nonhuman adenoviral vectors in human, murine, bovine, and porcine cells in culture
      Bangari, Dinesh S.; Shukla, Shruti; Mittal, Suresh K.
      Biochemical and Biophysical Research Communications (2005), 327 (3), 960-966CODEN: BBRCA9; ISSN:0006-291X. (Elsevier)
      Clin. usefulness of human Ad serotype 5 (HAd5) based vectors is limited primarily because of preexisting Ad immunity and lack of targeting to specific cell types. Alternative vectors based on less prevalent HAd serotypes as well as nonhuman adenoviruses such as porcine Ad serotype 3 (PAd3) and bovine Ad serotype 3 (BAd3) are being developed to overcome these shortcomings. Using virus neutralization assay, the authors examd. whether preexisting Ad immunity in humans would cross-neutralize PAd3 or BAd3. To further evaluate the potential of PAd3 and BAd3 vectors as gene delivery vehicles, we compared their transduction efficiencies in a panel of human, murine, bovine, and porcine cell lines to those obtained with a HAd5 vector. Transduction by the HAd5 vector in the majority of human cell lines correlated with the expression levels of coxsackievirus-adenovirus receptor (CAR), the primary HAd5 receptor; while transduction by PAd3 and BAd3 vectors was CAR-independent. The results suggest that PAd3 and BAd3 vectors are promising gene delivery vehicles for human gene therapy as well as for recombinant vaccines for human and animal use.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2MXksFGhtA%253D%253D&md5=571572a1ecfd5904257da7761ca83127
    137. 137
      Kümin, D.; Hofmann, C.; Rudolph, M.; Both, G. W.; Löser, P. Biology of Ovine Adenovirus Infection of Nonpermissive Cells. J. Virol. 2002, 76, 10882– 10893,  DOI: 10.1128/JVI.76.21.10882-10893.2002
      There is no corresponding record for this reference.
    138. 138
      Sinovac Says Its Covid-19 Vaccine Generated Immune Responses. STAT , 2020.
      There is no corresponding record for this reference.
    139. 139
      China’s Sinopharm Touts 100% Antibody Response for COVID-19 Vaccine It’s Already Giving to Workers. https://www.fiercepharma.com/pharma-asia/china-s-sinopharm-touts-100-antibody-response-for-covid-19-vaccine-it-s-already-giving (accessed 2020-07-27).
      There is no corresponding record for this reference.
    140. 140
      Chinese Researchers Launch Phase-2 Human Test for Possible Coronavirus Vaccine. Reuters Jun 21, 2020.
      There is no corresponding record for this reference.
    141. 141
      Zydus to Start Second Phase of Covid-19 Vaccine Candidate Trials Today. https://www.hindustantimes.com/india-news/zydus-to-start-second-phase-of-vaccine-candidate-trials-today/story-AkiC1iDUI9azdTSVbDFOQM.html (accessed 2020-08-10).
      There is no corresponding record for this reference.
    142. 142
      Keech, C.; Albert, G.; Cho, I.; Robertson, A.; Reed, P.; Neal, S.; Plested, J. S.; Zhu, M.; Cloney-Clark, S.; Zhou, H.; Smith, G.; Patel, N.; Frieman, M. B.; Haupt, R. E.; Logue, J.; McGrath, M.; Weston, S.; Piedra, P. A.; Desai, C.; Callahan, K. Phase 1–2 Trial of a SARS-CoV-2 Recombinant Spike Protein Nanoparticle Vaccine. N. Engl. J. Med. 2020, 0 (0), null,  DOI: 10.1056/NEJMoa2026920
      There is no corresponding record for this reference.
    143. 143
      Corum, J.; Grady, D.; Wee, S.-L.; Zimmer, C. Coronavirus Vaccine Tracker. New York Times , 2020.
      There is no corresponding record for this reference.
    144. 144
      Putin Announces First “Registered” COVID-19 Vaccine from Russia’s Gamaleya Institute; His Daughter among Those Inoculated - Health News, Firstpost. https://www.firstpost.com/health/putin-announces-first-registered-covid-19-vaccine-from-russias-gamaleya-institute-his-daughter-among-those-inoculated-8695031.html (accessed 2020-08-14).
      There is no corresponding record for this reference.
    145. 145
      Putin Says Russia has Approved “World First” Covid-19 Vaccine. But Questions Over Its Safety Remain. https://www.cnn.com/2020/08/11/europe/russia-coronavirus-vaccine-putin-intl/index.html (accessed 2020-08-14).
      There is no corresponding record for this reference.
    146. 146
      Hayashi, M.; Aoshi, T.; Haseda, Y.; Kobiyama, K.; Wijaya, E.; Nakatsu, N.; Igarashi, Y.; Standley, D. M.; Yamada, H.; Honda-Okubo, Y.; Hara, H.; Saito, T.; Takai, T.; Coban, C.; Petrovsky, N.; Ishii, K. J. Advax, a Delta Inulin Microparticle, Potentiates In-Built Adjuvant Property of Co-Administered Vaccines. EBioMedicine 2017, 15, 127– 136,  DOI: 10.1016/j.ebiom.2016.11.015
      146
      Advax, a Delta Inulin Microparticle, Potentiates In-built Adjuvant Property of Co-administered Vaccines
      Hayashi Masayuki; Aoshi Taiki; Haseda Yasunari; Kobiyama Kouji; Wijaya Edward; Standley Daron M; Nakatsu Noriyuki; Igarashi Yoshinobu; Yamada Hiroshi; Honda-Okubo Yoshikazu; Hara Hiromitsu; Saito Takashi; Takai Toshiyuki; Coban Cevayir; Petrovsky Nikolai; Ishii Ken J
      EBioMedicine (2017), 15 (), 127-136 ISSN:.
      Advax, a delta inulin-derived microparticle, has been developed as an adjuvant for several vaccines. However, its immunological characteristics and potential mechanism of action are yet to be elucidated. Here, we show that Advax behaves as a type-2 adjuvant when combined with influenza split vaccine, a T helper (Th)2-type antigen, but behaves as a type-1 adjuvant when combined with influenza inactivated whole virion (WV), a Th1-type antigen. In addition, an adjuvant effect was not observed when Advax-adjuvanted WV vaccine was used to immunize toll-like receptor (TLR) 7 knockout mice which are unable to respond to RNA contained in WV antigen. Similarly, no adjuvant effect was seen when Advax was combined with endotoxin-free ovalbumin, a neutral Th0-type antigen. An adjuvant effect was also not seen in tumor necrosis factor (TNF)-α knockout mice, and the adjuvant effect required the presences of dendritic cells (DCs) and phagocytic macrophages. Therefore, unlike other adjuvants, Advax potentiates the intrinsic or in-built adjuvant property of co-administered antigens. Hence, Advax is a unique class of adjuvant which can potentiate the intrinsic adjuvant feature of the vaccine antigens through a yet to be determined mechanism.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2sjjs12qtQ%253D%253D&md5=7af63ca16d7fc8389d93f22be67d7235
    147. 147
      Calcagnile, S.; Zuccotti, G. V. The Virosomal Adjuvanted Influenza Vaccine. Expert Opin. Biol. Ther. 2010, 10, 191– 200,  DOI: 10.1517/14712590903431014
      147
      The virosomal adjuvanted influenza vaccine
      Calcagnile Selma; Zuccotti Gian Vincenzo
      Expert opinion on biological therapy (2010), 10 (2), 191-200 ISSN:.
      IMPORTANCE OF THE FIELD: The protection conferred by influenza vaccines varies for several reasons, for example the age or degree of immune depression of the recipient. All currently available seasonal influenza vaccines are safe and substantially effective in preventing influenza in healthy people. However, elderly people and patients with chronic diseases or immune system defects need a more effective vaccine to avoid serious risks from influenza and its complications. Research has been undertaken to improve the efficacy of vaccination. Recent research includes the use of new adjuvants or antigen-presenting strategies. AREAS COVERED IN THIS REVIEW: The virosomal adjuvanted subunit influenza vaccine has been studied in groups for whom vaccination is recommended. We describe virosomal technology, including production and mode of action, as well as the available efficacy, immunogenicity and safety data, with the aim of understanding the benefits of this vaccine's use. WHAT THE READER WILL GAIN: A review of published data on efficacy, immunogenicity and safety from sponsor- and investigator- driven studies, focusing on recent publications. TAKE HOME MESSAGE: The vaccine was generally very immunogenic and safe in all investigated populations. Its ability to induce protective antibody titers has been shown to exceed that of conventional influenza vaccines in elderly people and individuals with little or no prior exposure to the viral strains.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC3c%252FksF2nsA%253D%253D&md5=1daeb8908c974e688026873457e471fa
    148. 148
      Garçon, N.; Vaughn, D. W.; Didierlaurent, A. M. Development and Evaluation of AS03, an Adjuvant System Containing α-Tocopherol and Squalene in an Oil-in-Water Emulsion. Expert Rev. Vaccines 2012, 11, 349– 366,  DOI: 10.1586/erv.11.192
      148
      Development and evaluation of AS03, an Adjuvant System containing αα-tocopherol and squalene in an oil-in-water emulsion
      Garcon, Nathalie; Vaughn, David W.; Didierlaurent, Arnaud M.
      Expert Review of Vaccines (2012), 11 (3), 349-366CODEN: ERVXAX; ISSN:1476-0584. (Expert Reviews Ltd.)
      A review. AS03 is an Adjuvant System composed of αα-tocopherol, squalene and polysorbate 80 in an oil-in-water emulsion. In various nonclin. and clin. studies, high levels of antigen-specific antibodies were obtained after administration of an AS03-adjuvanted vaccine, permitting antigen-sparing strategies. AS03 has been shown to enhance the vaccine antigen-specific adaptive response by activating the innate immune system locally and by increasing antigen uptake and presentation in draining lymph nodes, a process that is modulated by the presence of αα-tocopherol in AS03. In nonclin. models of the AS03-adjuvanted prepandemic H5N1 influenza vaccine, increased levels of anti-influenza antibody afforded protection against disease and against virus replication of influenza strains homologous and heterologous to the vaccine strain. By incorporating AS03 in the pandemic H1N1/2009 vaccine, vaccine immunogenicity was increased compared with nonadjuvanted H1N1 vaccines. High H1N1/2009/AS03 vaccine effectiveness was demonstrated in several assessments in multiple populations. Altogether, the nonclin. and clin. data illustrate the ability of AS03 to induce superior adaptive responses against the vaccine antigen, principally in terms of antibody levels and immune memory. In general, these results support the concept of Adjuvant Systems as a plausible approach to develop new effective vaccines.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XjtlOjtLY%253D&md5=3736be68e96e9e37d3aa7c5733a5b23d
    149. 149
      A Phase 1, Randomized, Double-Blind, Placebo-Controlled, First-in-Human Study to Evaluate the Safety and Immunogenicity of SCB 2019, a Recombinant SARS-CoV-2 Trimeric S Protein Subunit Vaccine for COVID-19 in Healthy Volunteers - Full Text View. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT04405908 (accessed 2020-08-03).
      There is no corresponding record for this reference.
    150. 150
      A Randomized, Partially-Blinded, Dose-Ranging Phase 1 Study to Assess the Safety, Tolerability, and Immunogenicity of a Recombinant Coronavirus-Like Particle COVID 19 Vaccine in Adults 18–55 Years of Age - Full Text View. ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT04450004 (accessed 2020-08-03).
      There is no corresponding record for this reference.
    151. 151
      Sanofi: Press Releases, Tuesday, April 14, 2020. https://www.sanofi.com/media-room/press-releases/2020/2020-04-14 13–00–00 2015521 (accessed 2020-08-03).
      There is no corresponding record for this reference.
    152. 152
      GSK Allies with Innovax for COVID-19 Vaccine R&D Project. https://www.fiercebiotech.com/biotech/gsk-allies-innovax-for-covid-19-vaccine-r-d-project (accessed 2020-04-09).
      There is no corresponding record for this reference.
    153. 153
      GSK Makes Adjuvant Available to Coronavirus Vaccine Project. https://www.fiercebiotech.com/biotech/gsk-makes-adjuvant-available-to-coronavirus-vaccine-project (accessed 2020-08-03).
      There is no corresponding record for this reference.
    154. 154
      Campbell, J. D. Development of the CpG Adjuvant 1018: A Case Study. Methods Mol. Biol. 2017, 1494, 15– 27,  DOI: 10.1007/978-1-4939-6445-1_2
      154
      Development of the CpG adjuvant 1018: a case study
      Campbell, John D.
      Methods in Molecular Biology (New York, NY, United States) (2017), 1494 (Vaccine Adjuvants), 15-27CODEN: MMBIED; ISSN:1940-6029. (Springer)
      The development of aluminum salts (alum) as vaccine adjuvants was an empirical process with little understanding of the mechanism of action and, with decades of use, it has become clear that there is a need for alternatives where alum-based adjuvants are suboptimal. Oligonucleotides contg. unmethylated CpG sequences represent one alternative as they are potent stimulators of the vertebrate innate immune system through activation of Toll-like receptor-9. This chapter outlines the methods used by Dynavax Technologies to progress a CpG-contg. oligonucleotide sequence termed 1018 through preclin. and clin. testing as an adjuvant for immunization against hepatitis B virus (HBV). 1018 Is a short (22-mer) oligonucleotide sequence contg. CpG motifs active in both rodents and primates. Preclin. testing of hepatitis B surface antigen (HBsAg) + 1018 in comparison to HBsAg + alum demonstrated induction of substantially higher antibody titers and a favorable safety profile for 1018. Most importantly, clin. studies with HBsAg vaccination consistently demonstrate more rapid induction of protective antibody titers with 1018 compared to alum in all populations studied, including groups that are harder to immunize such as the elderly and immunocompromised individuals. These studies represent the basis for use of the CpG-motif-contg. oligonucleotide 1018 as an improved adjuvant for HBsAg immunogenicity. HBsAg + 1018 (HEPLISAV-B ) is currently in late-stage clin. testing for prophylactic immunization against HBV.
      >> More from SciFinder ®
      https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhvFWisLvM&md5=bd1b425b5696f78ad5e937544062bf9a
    155. 155
      A Phase I, Prospective, Open-Labeled Study to Evaluate the Safety and Immunogenicity of MVC-COV1901 - Full Text View. ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT04487210 (accessed 2020-08-03).
      There is no corresponding record for this reference.
    156. 156
      Dynavax and Sinovac Announce Collaboration to Develop a Coronavirus (COVID-19) Vaccine. Dynavax Technologies Corp.https://investors.dynavax.com/news-releases/news-release-details/dynavax-and-sinovac-announce-collaboration-develop-coronavirus (accessed 2020-08-03).
      There is no corresponding record for this reference.
    157. 157
      Valneva and Dynavax Announce Collaboration to Advance Vaccine Development for COVID-19. Valneva. https://valneva.com/press-release/valneva-and-dynavax-announce-collaboration-to-advance-vaccine-development-for-covid-19/ (accessed 2020-08-03).
      There is no corresponding record for this reference.

  • Supporting Information

    Supporting Information

    ARTICLE SECTIONS
    Jump To

    The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acsnano.0c07197.

    • Data table summarizing COVID-19 vaccines and their type, developer, and status (Table S1) (PDF)


    Terms & Conditions

    Most electronic Supporting Information files are available without a subscription to ACS Web Editions. Such files may be downloaded by article for research use (if there is a public use license linked to the relevant article, that license may permit other uses). Permission may be obtained from ACS for other uses through requests via the RightsLink permission system: http://pubs.acs.org/page/copyright/permissions.html.

PDF [ 3MB]

Pair your accounts.

Export articles to Mendeley

Get article recommendations from ACS based on references in your Mendeley library.

Pair your accounts.

Export articles to Mendeley

Get article recommendations from ACS based on references in your Mendeley library.

You’ve supercharged your research process with ACS and Mendeley!

STEP 1:
Click to create an ACS ID

Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

MENDELEY PAIRING EXPIRED
Your Mendeley pairing has expired. Please reconnect