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SARS-CoV-2 Vaccines

Educational Objective
To identify the key insights or developments described in this article
1 Credit 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
1.
Du  L , He  Y , Zhou  Y ,  et al.  The spike protein of SARS-CoV—a target for vaccine and therapeutic development.   Nat Rev Microbiol. 2009;7(3):226-236.PubMedGoogle ScholarCrossref
2.
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.PubMedGoogle Scholar
3.
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.PubMedGoogle Scholar
4.
Zimmermann  P , Curtis  N .  Factors that influence the immune response to vaccination.   Clin Microbiol Rev. 2019;32(2):e00084-18.PubMedGoogle Scholar
5.
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
6.
Tatsis  N , Ertl  HC .  Adenoviruses as vaccine vectors.   Mol Ther. 2004;10(4):616-629.PubMedGoogle ScholarCrossref
7.
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.PubMedGoogle ScholarCrossref
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