Prospects for a safe COVID-19 vaccine
Abstract
Rapid development of an efficacious vaccine against the viral pathogen severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the cause of the coronavirus disease 2019 (COVID-19) pandemic, is essential, but rigorous studies are required to determine the safety of candidate vaccines. Here, on behalf of the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) Working Group, we evaluate research on the potential risk of immune enhancement of disease by vaccines and viral infections, including coronavirus infections, together with emerging data about COVID-19 disease. Vaccine-associated enhanced disease has been rarely encountered with existing vaccines or viral infections. Although animal models of SARS-CoV-2 infection may elucidate mechanisms of immune protection, we need observations of enhanced disease in people receiving candidate COVID-19 vaccines to understand the risk of immune enhancement of disease. Neither principles of immunity nor preclinical studies provide a basis for prioritizing among the COVID-19 vaccine candidates with respect to safety at this time. Rigorous clinical trial design and postlicensure surveillance should provide a reliable strategy to identify adverse events, including the potential for enhanced severity of COVID-19 disease, after vaccination.
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Science Translational Medicine
Volume 12 | Issue 568
November 2020
November 2020
Copyright
Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
This is an article distributed under the terms of the Science Journals Default License.
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Submission history
Received: 30 July 2020
Accepted: 16 October 2020
Acknowledgments
We acknowledge T. Shimabukuro and N. Messonnier of the U.S. Centers for Disease Control and Prevention for the helpful discussions, and W. Edwards of the Duke Human Vaccine Institute and B. Tolman of Deloitte Consulting LLP for editorial assistance. We thank the ACTIV Working Group whose nonauthor members include P. Annunziato, Merck & Co. Inc.; B. Bell, University of Washington; S. Buchbinder, University of California, San Francisco and San Francisco Department of Public Health; M. Cavaleri, European Medicines Agency; M. Davis, Stanford University School of Medicine; E. Emini, Bill & Melinda Gates Foundation; G. Glenn, Novavax Inc.; E. Hanon, GlaxoSmithKline; K. Jansen, Pfizer; A. Lanzavecchia, Vir Biotechnology Inc. and Institute for Research in Biomedicine; D. Lowy, National Cancer Institute, NIH; P. Marks, FDA; J. Mascola, National Institute of Allergy and Infectious Diseases, NIH; N. Messonnier, U.S. Centers for Disease Control and Prevention; N. Michael, Walter Reed Army Institute of Research; P. Offit, University of Pennsylvania; J. Seals, Biomedical Advanced Research and Development Authority, Health and Human Services; J. Tartaglia, Sanofi Pasteur; T. Villafana, AstraZeneca; T. Zaks, Moderna Inc. Competing interests: B.F.H. is a coinventor on patent applications for COVID-19 vaccine designs. P.J.H. is developing a low-cost COVID-19 vaccine that has been licensed to a pharmaceutical company for manufacture. S.R. is currently employed by Sanofi, which is pursuing therapeutic and vaccine development to treat COVID-19. H.S. is an employee and shareholder of Johnson & Johnson, which is developing a COVID-19 vaccine. M.W. is currently employed by Moderna Inc., which is pursuing therapeutic and vaccine development to treat COVID-19. A.A. is a consultant for Vir Biotechnology. The other authors declare that they have no competing interests. Data and materials availability: All data associated with this study are present in the paper.
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- Barton F. Haynes et al.
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RE: Postlicensure surveillance and the immunity assessment test after COVID-19 vaccine
To The Editor:
Haynes et al. (1) proposed the importance of postlicensure surveillance after COVID-19 vaccine.
The Pfizer and BioNTech vaccine has passed safety and efficacy tests and has been approved in the UK on December 2, 2020. How long will vaccine-induced immunity last? There is no quick way to define how long immunity to the SARS-CoV-2 virus will last, and physicians will need to monitor the immunity closely.
How to monitor immunity after COVID-19 vaccine? Food and Drug Administration (FDA) has issued emergency use authorization (EUA) for clinical application of SARS-CoV-2 serologic tests (2). There are three classes of targets used in EUA authorized serology tests: Nucleocapsid, Spike, and Spike & Nucleocapsid.
How to choose immunity test after COVID-19 vaccination? Grifoni et al. (3) first reported that IgG titers of SARS-CoV-2 RBD correlated with Spike-specific CD4 and CD8 T cells. Since the Pfizer and BioNTech vaccine encodes the RBD of the SARS-CoV-2 (4) and the RBD region is a critical target for neutralizing antibodies (5), the IgG titer of SARS-CoV-2 RBD may reflect how long the immunity to SARS-CoV-2 will last.
Antibodies of different subclasses activate different effector mechanisms in response to SARS-CoV-2 RBD antigens. The detection of anti-RBD subtypes is also important for the immunity of clinical research (5).
Nucleocapsid as a target approved in EUA authorized serology tests has showed constitute false-positive reactions due to sample cross-reactivity to Nucleocapsid (6). Grzelak et al (7) also found that the false-positive rate of COVID-19 in antibody testing with a SARS-CoV-2 Nucleocapsid is about 4.7%.
The disease severity of COVID-19 is associated with the titers of anti-Nucleocapsid or anti-Spike & Nucleocapsid antibodies (1). It has been reported that the titer of IgM and IgG against the SARS-CoV-2 Nucleocapsid or Spike & Nucleocapsid is higher in severe and fatal cases of COVID-19 (1). However, the study did not separately test the titer of anti-Nucleocapsid or anti-Spike. Furthermore, there are a limited number of studies in the titer of anti-RBD antibodies and the subtype of antibodies associated to the severity of COVID-19, which might be related to the immunity after COVID-19 vaccination (3, 4).
In summary, the IgG titer of SARS-CoV-2 RBD and the neutralization titer of SARS-CoV-2 might be valuable immunity assessment tests (4).
References
1. B. F. Haynes et al. Prospects for a safe COVID-19 vaccine. Sci. Transl. Med. 12, eabe0948 (2020). doi: 10.1126/scitranslmed.abe0948.
2. EUA authorized serology test performance. https://www.fda.gov/medical-devices/coronavirus-disease-2019-covid-19-em... (accessed December 6, 2020).
3. A. Grifoni et al. Targets of T cell responses to SARS-CoV-2 coronavirus in humans with COVID-19 disease and unexposed individuals. Cell 181, 1489–1501.e15 (2020). doi:10.1016/j.cell.2020.05.015pmid:32473127.
4. U. Sahin et al. COVID-19 vaccine BNT162b1 elicits human antibody and TH1 T cell responses. Nature 586, 594–599 (2020).
5. Q. Zeng et al. Tackling COVID19 by exploiting pre-existing cross-reacting spike-specific immunity. Mol Ther. 28 (11), 2314–2315 (2020).
6. C. Rosadas et al. Testing for responses to the wrong SARS-CoV-2 antigen? Lancet 396, E23 (2020). doi: 10.1016/S0140-6736(20)31830-4.
7. L. Grzelak, et al, A comparison of four serological assays for detecting anti–SARS-CoV-2 antibodies in human serum samples from different populations. Sci. Transl. Med. 12, eabc3103 (2020). doi: 10.1126/scitranslmed.abc3103.
RE: Safety et al. Requirements for COVID-19 Vaccines
In addition to a safe vaccine for COVID-29, it is also important that a viable vaccine is effective, tolerable, immunogenic, durable, affordable, ethically approved, widely distributed, and fast acting, preferably with a single injection to prevent infection between the first and second doses.
Otherwise, any intended global public healthcare approach to achieve herd immunity, mitigation, or unlikely elimination of the virus and associated disease will not be achieved.