Skip to main content
SpringerLink
Log in

SARS-COV-2 and Other mRNA Vaccines

  • Chapter
  • First Online:
Messenger RNA Therapeutics

Part of the book series: RNA Technologies ((RNATECHN,volume 13))

  • 1042 Accesses

Abstract

Advances in our biological understanding of mRNA and ionizable-lipid-based nanoparticles (LNP) for delivery have allowed their application as vaccines for the prevention of SARS-COV-2 disease following unprecedented speed of development through to emergency use licensure in around three hundred days from virus sequence availability. Case studies of three SARS-COV-2 mRNA vaccines for which field clinical efficacy data are available are examined and related to mRNA/LNP attributes where possible. The status of other SARS-COV-2 and non-SARS-COV-2 mRNA vaccines in clinical development and select future prospective innovations are reviewed.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Al Kaabi N, Zhang Y, Xia S et al (2021) Effect of 2 inactivated SARS-COV-2 vaccines on symptomatic COVID-19 infection in adults: a randomized clinical trial. JAMA 326:35–45

    Article  CAS  PubMed  Google Scholar 

  • Anderson EJ, Rouphael NG, Widge AT et al (2020) Safety and immunogenicity of SARS-COV-2 mRNA-1273 vaccine in older adults. N Engl J Med 383:2427–2438

    Article  CAS  PubMed  Google Scholar 

  • Baden LR, El Sahly HM, Essink B et al (2021) Efficacy and safety of the mRNA-1273 SARS-COV-2 vaccine. N Engl J Med 384:403–416

    Article  CAS  PubMed  Google Scholar 

  • Baiersdörfer M, Boros G, Muramatsu H et al (2019) A facile method for the removal of dsRNA contaminant from in vitro-transcribed mRNA. Mol Ther Nucleic Acids 15:26–35

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Barda N, Dagan N, Ben-Shlomo Y et al (2021) Safety of the BNT162b2 mRNA covid-19 vaccine in a nationwide setting. N Engl J Med 385:1078–1090

    Article  CAS  PubMed  Google Scholar 

  • Baronti L, Karlsson H, Marušič M et al (2018) A guide to large-scale RNA sample preparation. Anal Bioanal Chem 410:3239–3252

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Blakney AK, Ip S, Geall AJ (2021) An update on self-amplifying mRNA vaccine development. Vaccines (Basel) 9(2)

    Google Scholar 

  • Blumenthal KG, Phadke NA, Bates DW (2021) Safety surveillance of COVID-19 mRNA vaccines through the vaccine safety datalink. JAMA 326:1375–1377

    Article  CAS  PubMed  Google Scholar 

  • Bozkurt B, Kamat I, Hotez PJ (2021) Myocarditis with COVID-19 mRNA vaccines. Circulation 144:471–484

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Buschmann MD, Carrasco MJ, Alishetty S et al (2021) Nanomaterial delivery systems for mRNA vaccines. Vaccines (Basel) 9(1)

    Google Scholar 

  • Caforio AL, Pankuweit S, Arbustini E et al (2013) Current state of knowledge on aetiology, diagnosis, management, and therapy of myocarditis: a position statement of the European society of cardiology working group on myocardial and pericardial diseases. Eur Heart J 34(2636–2648):2648a–2648d

    Google Scholar 

  • Chandler RE (2020) Optimizing safety surveillance for COVID-19 vaccines. Nat Rev Immunol 20:451–452

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Choi A, Koch M, Wu K et al (2021) Safety and immunogenicity of SARS-COV-2 variant mRNA vaccine boosters in healthy adults: an interim analysis. Nat Med 27:2025–2031

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chu L, McPhee R, Huang W et al (2021) A preliminary report of a randomized controlled phase 2 trial of the safety and immunogenicity of mRNA-1273 SARS-COV-2 vaccine. Vaccine 39:2791–2799

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cromer D, Reynaldi A, Steain M et al (2021) Relating in vitro neutralisation level and protection in the CVnCoV (CUREVAC) trial. medRxiv, 2021.2006.2029.21259504

    Google Scholar 

  • Curevac/Press-release (2021a) CureVac press release, CureVac to shift focus of COVID-19 vaccine development to second generation mRNA technology

    Google Scholar 

  • Curevac/Protocol (2021b) CureVac phase 2b/3 clinical trial protocol (CV-NCOV-004), version 3

    Google Scholar 

  • Earle KA, Ambrosino DM, Fiore-Gartland A et al (2021) Evidence for antibody as a protective correlate for COVID-19 vaccines. Vaccine 39:4423–4428

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • EMA/News (2021) EMA raises awareness of clinical care recommendations to manage suspected thrombosis with thrombocytopenia syndrome. European medicines agency

    Google Scholar 

  • Falsey AR, Frenck RW Jr, Walsh EE et al (2021) SARS-COV-2 neutralization with BNT162b2 vaccine dose 3. N Engl J Med 385:1627–1629

    Article  PubMed  Google Scholar 

  • Furqan MM, Verma BR, Cremer PC et al (2021) Pericardial diseases in COVID19: a contemporary review. Curr Cardiol Rep 23:90

    Article  PubMed  PubMed Central  Google Scholar 

  • Gargano JW, Wallace M, Hadler SC et al (2021) Use of mRNA COVID-19 vaccine after reports of myocarditis among vaccine recipients: update from the advisory committee on immunization practices—United States, June 2021. MMWR Morb Mortal Wkly Rep 70:977–982

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gennova (2021) Home page. https://gennova.bio/mrna-vaccines/

  • Gilbert SC (2012) T-cell-inducing vaccines—what’s the future. Immunology 135:19–26

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • GISAID (2021) Global initiative on sharing avian influenza data (GISAID), tracking of variants

    Google Scholar 

  • Greenlight/Report (2021) Greenlight biosciences, a blueprint to vaccinate the world

    Google Scholar 

  • Hassett KJ, Benenato KE, Jacquinet E et al (2019) Optimization of lipid nanoparticles for intramuscular administration of mRNA vaccines. Mol Ther Nucleic Acids 15:1–11

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Heath PT, Galiza EP, Baxter DN et al (2021) Safety and efficacy of NVX-CoV2373 covid-19 vaccine. N Engl J Med 385:1172–1183

    Article  CAS  PubMed  Google Scholar 

  • Hippisley-Cox J, Patone M, Mei XW et al (2021) Risk of thrombocytopenia and thromboembolism after covid-19 vaccination and SARS-COV-2 positive testing: self-controlled case series study. BMJ 374:n1931

    Article  PubMed  Google Scholar 

  • Huber SA (2016) Viral myocarditis and dilated cardiomyopathy: etiology and pathogenesis. Curr Pharm Des 22:408–426

    Article  CAS  PubMed  Google Scholar 

  • Igyártó BZ, Jacobsen S, Ndeupen S (2021) Future considerations for the mRNA-lipid nanoparticle vaccine platform. Curr Opin Virol 48:65–72

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • IVAC (2021) International vaccine access center, John Hopkins Bloomberg School of Public Health, VIEW-Hub. www.view-hub.org. Accessed Oct 10 2021

  • Jackson LA, Anderson EJ, Rouphael NG et al (2020) An mRNA vaccine against SARS-COV-2—preliminary report. N Engl J Med 383:1920–1931

    Article  CAS  PubMed  Google Scholar 

  • Kamphuis E, Junt T, Waible Z et al (2006) Type I interferons directly regulate lymphocyte recirculation and cause transient blood lymphopenia. Blood 108:3253–3261

    Article  CAS  PubMed  Google Scholar 

  • Kapoor Y, Meyer RF, Meyer BK et al (2021) Flexible manufacturing: the future state of drug product development and commercialization in the pharmaceutical industry. J Pharm Innov 16:2–10

    Article  Google Scholar 

  • Kis Z, Kontoravdi C, Dey AK et al (2020) Rapid development and deployment of high-volume vaccines for pandemic response. J Adv Manuf Process 2:e10060

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Klein NP, Lewis N, Goddard K et al (2021) Surveillance for adverse events after COVID-19 mRNA vaccination. JAMA 326:1390–1399

    Article  CAS  PubMed  Google Scholar 

  • Kremsner PG, Mann P, Kroidl A et al (2021) Safety and immunogenicity of an mRNA-lipid nanoparticle vaccine candidate against SARS-COV-2: a phase 1 randomized clinical trial. Wien Klin Wochenschr 133:931–941

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kremsner PG, Guerrero RAA, Arana-Arri E et al (2021) Efficacy and safety of the CVnCoV SARS-COV-2 mRNA vaccine candidate: results from Herald, a Phase 2b/3, randomised, observer-blinded, placebo-controlled clinical trial in ten countries in Europe and Latin America. Lancet Infect Dis https://doi.org/10.1016/S1473-3099(21)00677-0

  • Larson KF, Ammirati E, Adler ED et al (2021) Myocarditis after BNT162b2 and mRNA-1273 vaccination. Circulation 144:506–508

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu Y, Liu J, Xia H et al (2021a) Neutralizing activity of BNT162b2-elicited serum. N Engl J Med 384:1466–1468

    Article  PubMed  Google Scholar 

  • Liu Y, Liu J, Xia H et al (2021b) BNT162b2-Elicited neutralization against new SARS-COV-2 spike variants. N Engl J Med 385:472–474

    Article  PubMed  Google Scholar 

  • Logunov DY, Dolzhikova IV, Shcheblyakov DV et al (2021) Safety and efficacy of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine: an interim analysis of a randomised controlled phase 3 trial in Russia. Lancet 397:671–681

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Low JG, de Alwis R, Chen S et al (2021) A phase 1/2 randomized, double-blinded, placebo controlled ascending dose trial to assess the safety, tolerability and immunogenicity of ARCT-021 in healthy adults. medRxiv 2021.2007.2001.21259831

    Google Scholar 

  • Lukavsky PJ, Puglisi JD (2004) Large-scale preparation and purification of polyacrylamide-free RNA oligonucleotides. RNA 10:889–893

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • McKay PF, Hu K, Blakney AK et al (2020) Self-amplifying RNA SARS-COV-2 lipid nanoparticle vaccine candidate induces high neutralizing antibody titers in mice. Nat Commun 11:3523

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Mevorach D, Anis E, Cedar N et al (2021) Myocarditis after BNT162b2 mRNA vaccine against covid-19 in Israel. N Engl J Med. https://doi.org/10.1056/NEJMoa2109730

    Article  PubMed  PubMed Central  Google Scholar 

  • Modern/Investor-relations (2021a) Moderna’s other vaccines: CMV vaccine (mRNA-1647). https://investors.modernatx.com/static-files/693ffcac-b2fc-4f7e-91c5-0a9164e7c6dc

  • Moderna/Press-release (2021) Moderna press release, moderna announces FDA advisory committee unanimously votes in support of Emergency use for a booster dose of moderna’s COVID-19 vaccine in the US. https://investors.modernatx.com/news-releases/news-release-details/moderna-announces-fda-advisory-committee-unanimously-votes

  • Moderna/Press-release (2021a) Moderna press release, moderna announces clinical progress from its industry-leading mRNA vaccine franchise and continues investments to accelerate pipeline development. https://investors.modernatx.com/news-releases/news-release-details/moderna-announces-clinical-progress-its-industry-leading-mrna

  • Mulligan MJ, Lyke KE, Kitchin N et al (2020) Phase I/II study of COVID-19 RNA vaccine BNT162b1 in adults. Nature 586:589–593

    Article  CAS  PubMed  Google Scholar 

  • Pan J, Mendes LP, Yao M et al (2019) Polyamidoamine dendrimers-based nanomedicine for combination therapy with siRNA and chemotherapeutics to overcome multidrug resistance. Eur J Pharm Biopharm 136:18–28

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Perche F, Gosset D, Méve M et al (2011) Selective gene delivery in dendritic cells with mannosylated and histidylated lipopolyplexes. J Drug Target 19:315–325

    Article  CAS  PubMed  Google Scholar 

  • Planas D, Veyer D, Baidaliuk A et al (2021) Reduced sensitivity of SARS-COV-2 variant delta to antibody neutralization. Nature 596:276–280

    Article  CAS  PubMed  Google Scholar 

  • Polack FP, Thomas SJ, Kitchin N et al (2020) Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N Engl J Med 383:2603–2615

    Article  CAS  PubMed  Google Scholar 

  • Pollock KM, Cheeseman HM, Szubert AJ et al (2021) Safety and immunogenicity of a self-amplifying RNA Vaccine against COVID-19: COVAC1, a Phase I, dose-ranging trial. Lancet. Available at SSRN https://ssrn.com/abstract=3859294 or https://doi.org/10.2139/ssrn.3859294

  • Pottegård A, Lund LC, Karlstad Ø et al (2021) Arterial events, venous thromboembolism, thrombocytopenia, and bleeding after vaccination with oxford-AstraZeneca ChAdOx1-S in Denmark and Norway: population based cohort study. BMJ 373:n1114

    Article  PubMed  Google Scholar 

  • Rosa SS, Prazeres DMF, Azevedo AM et al (2021) mRNA vaccines manufacturing: challenges and bottlenecks. Vaccine 39:2190–2200

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sadoff J, Gray G, Vandebosch A et al (2021) Safety and efficacy of single-dose Ad26.COV2.S vaccine against covid-19. N Engl J Med 384:2187–2201

    Article  CAS  PubMed  Google Scholar 

  • Sahin U, Muik A, Derhovanessian E et al (2020a) COVID-19 vaccine BNT162b1 elicits human antibody and TH1 T cell responses. Nature 586:594–599

    Article  CAS  PubMed  Google Scholar 

  • Sahin U, Muik A, Vogle, I et al (2020b) BNT162b2 induces SARS-COV-2-neutralising antibodies and T cells in humans. medRxiv, 2020b.2012.2009.20245175

    Google Scholar 

  • Salleh MZ, Derrick JP, Deris ZZ (2021) Structural evaluation of the spike glycoprotein variants on SARS-COV-2 transmission and immune evasion. Int J Mol Sci 22:7425

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schulze J, Rentzsch M, Kim D et al (2019) A liposomal platform for delivery of a protein antigen to langerin-expressing cells. Biochemistry 58:2576–2580

    Article  CAS  PubMed  Google Scholar 

  • Tam YY, Chen S, Zaifman J et al (2013) Small molecule ligands for enhanced intracellular delivery of lipid nanoparticle formulations of siRNA. Nanomedicine 9:665–674

    Article  CAS  PubMed  Google Scholar 

  • Tanriover MD, Doğanay HL, Akov M et al (2021) Efficacy and safety of an inactivated whole-virion SARS-COV-2 vaccine (CoronaVac): interim results of a double-blind, randomised, placebo-controlled, phase 3 trial in Turkey. Lancet 398:213–222

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Uddin MN, Roni MA (2021). Challenges of storage and stability of mRNA-based COVID-19 vaccines. Vaccines (Basel) 9(9)

    Google Scholar 

  • US/CDC (2021) Cases of cerebral venous sinus thrombosis with thrombocytopenia after receipt of the Johnson & Johnson COVID-19 vaccine. Centers for disease control and prevention. https://emergency.cdc.gov/han/2021/han00442.asp

  • US/CDC/Clinical-considerations (2021) U.S. CDC, national center for immunization and respiratory diseases, clinical considerations: myocarditis and pericarditis after receipt of mRNA COVID-19 vaccines among adolescents and young adults. https://www.cdc.gov/vaccines/covid-19/clinical-considerations/myocarditis.html

  • US/CDC/VAERS (2021) US CDC Awardee COVID-19 vaccination planning meeting, Su JR Myopericarditis following COVID-19 vaccination: updates from the vaccine adverse event reporting system (VAERS)

    Google Scholar 

  • van Gils MJ, Lavell AHA, van der Straten K et al (2021) Four SARS-COV-2 vaccines induce quantitatively different antibody responses against SARS-COV-2 variants. medRxiv 2021.2009.2027.21264163

    Google Scholar 

  • VRBPAC/Moderna (2020) Vaccines and related biological products advisory committee, briefing document, moderna (mRNA-1273). https://www.fda.gov/media/152953/download

  • VRBPAC/Pfizer-BioNTech (2020) Vaccine and related biological product advisory committee, briefing document, Pfizer-BioNTech COVID-19 (BNT162, PF-07302048). https://www.fda.gov/media/144246/download

  • Walsh EE, Frenck RW Jr, Falsey AR et al (2020) Safety and immunogenicity of two RNA-based covid-19 vaccine candidates. N Engl J Med 383:2439–2450

    Article  CAS  PubMed  Google Scholar 

  • Wesselhoeft RA, Kowalsk PS, Anderson DG (2018) Engineering circular RNA for potent and stable translation in eukaryotic cells. Nat Commun 9:2629

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Wesselhoeft RA, Kowalski P, Parker-Hale FC et al (2019) RNA circularization diminishes immunogenicity and can extend translation duration in vivo. Mol Cell 74:508-520.e504

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • WHO/Joint-Press-Release (2021) Global leaders commit further support for global equitable access to COVID-19 vaccines and COVAX. https://www.who.int/news/item/23-09-2021-global-leaders-commit-further-support-for-global-equitable-access-to-covid-19-vaccines-and-covax

  • Witberg G, Barda N, Hos S et al (2021) Myocarditis after Covid-19 vaccination in a large health care organization. N Engl J Med 385:2132–2139

    Article  CAS  PubMed  Google Scholar 

  • Witzigmann D, Kulkarni JA, Leung J et al (2020) Lipid nanoparticle technology for therapeutic gene regulation in the liver. Adv Drug Deliv Rev 159:344–363

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wu K, Werner AP, Moliva JI et al (2021) mRNA-1273 vaccine induces neutralizing antibodies against spike mutants from global SARS-COV-2 variants. bioRxiv. https://doi.org/10.1101/2021.01.25.427948

Download references

Author information

Authors and Affiliations

  1. Clover Biopharmaceuticals, Research and Development, London, UK

    Nicholas Jackson

Authors
  1. Nicholas Jackson
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nicholas Jackson .

Editor information

Editors and Affiliations

  1. NanoBioMedical Center, Adam Mickiewicz University, Poznań, Poland

    Stefan Jurga

  2. NanoBioMedical Center, Adam Mickiewicz University, Poznań, Poland

    Jan Barciszewski

Rights and permissions

Reprints and permissions

Copyright information

© 2022 The Author(s), under exclusive license to Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Jackson, N. (2022). SARS-COV-2 and Other mRNA Vaccines. In: Jurga, S., Barciszewski, J. (eds) Messenger RNA Therapeutics. RNA Technologies, vol 13. Springer, Cham. https://doi.org/10.1007/978-3-031-08415-7_6

Download citation

Publish with us

Policies and ethics

Search

Navigation