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Read Article Claim CME

Shortly after SARS-CoV emerged at the turn of the 21st century, the spike (S) protein (particularly in its prefusion [native] conformation) was identified as the immunodominant antigen of the virus.¹ Evaluation of patients with SARS-CoV-2 revealed that binding and neutralizing antibodies primarily target the receptor-binding domain of the S1 subunit.² Once this putative vaccine target was identified, the next challenge was how to best generate an effective immune response to SARS-CoV-2. The characteristics of this response would include production of neutralizing antibodies, generation of a T-cell response, and avoidance of immune-enhanced disease (vaccine-induced response that led to paradoxically increased disease severity on viral challenge).³

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Article Information

Corresponding Author: C. Buddy Creech MD, MPH, Division of Infectious Diseases, Vanderbilt University School of Medicine, D-7235 MCN, Nashville, TN 37232-2581 (buddy.creech@vanderbilt.edu).

Published Online: February 26, 2021. doi:10.1001/jama.2021.3199

Correction: This article was corrected on March 23, 2021, to fix EUA information in the Table for the Moderna, Pfizer-BioNTech, and Janssen/Johnson & Johnson vaccines.

Conflict of Interest Disclosures: Dr Creech reported receiving personal fees from Altimmune for vaccine development and from Horizon for care of children with chronic granulomatous disease; grants from Merck for Clostridioides difficile treatment and from GlaxoSmithKline for Staphylococcus aureus vaccine development; and personal fees from Premier Healthcare for vaccine education, Astellas for serving on a vaccine study data and safety monitoring board, Karius Diagnostics, and Vir Biotechnology for monoclonal antibody development outside the submitted work. No other disclosures were reported.

References

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Premkumar L , Segovia-Chumbez B , Jadi R , et al. The receptor binding domain of the viral spike protein is an immunodominant and highly specific target of antibodies in SARS-CoV-2 patients. Sci Immunol. 2020;5(48):eabc8413.PubMed Google Scholar

Tseng CT , Sbrana E , Iwata-Yoshikawa N , et al. Immunization with SARS coronavirus vaccines leads to pulmonary immunopathology on challenge with the SARS virus. PLoS One. 2012;7(4):e35421.PubMed Google Scholar

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Novavax COVID-19 vaccine demonstrates 89.3% efficacy in UK phase 3 trial. News release. January 28, 2021. Accessed February 21, 2021. https://ir.novavax.com/news-releases/news-release-details/novavax-covid-19-vaccine-demonstrates-893-efficacy-uk-phase-3

Tatsis N , Ertl HC . Adenoviruses as vaccine vectors. Mol Ther. 2004;10(4):616-629.PubMed Google Scholar Crossref

Zak DE , Andersen-Nissen E , Peterson ER , et al. Merck Ad5/HIV induces broad innate immune activation that predicts CD8⁺ T-cell responses but is attenuated by preexisting Ad5 immunity. Proc Natl Acad Sci U S A. 2012;109(50):e3503-e3512.PubMed Google Scholar Crossref

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