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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

SARS-CoV-2 Vaccines

The Public Can Trust the FDA’s Vaccine Review Process

SARS-CoV-2 Vaccines and the Growing Threat of Viral Variants

Patient Information: Necessity of 2 Doses of the Pfizer and Moderna COVID-19 Vaccines

The US Regulatory System and COVID-19 Vaccines

The Challenge of Conducting Placebo-Controlled Trials as COVID-19 Vaccines Become Authorized

Antibody Titers After a Single Vaccine Dose in Health Care Workers Previously Infected With SARS-CoV-2

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Immunogenicity of a Single Dose of SARS-CoV-2 mRNA Vaccine in Solid Organ Transplant Recipients

Incentivizing Vaccination Uptake: The “Green Pass” Proposal in Israel

Adverse Reactions in the US to mRNA-Based Coronavirus Vaccines

Experts Discuss COVID-19—Variants and Vaccine Efficacy, Immunosuppressed Patients, and More

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Antibody Titers After a Single Vaccine Dose in Health Care Workers Previously Infected With SARS-CoV-2

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COVID-19 in 2021—Continuing Uncertainty

Acute Allergic Reactions to mRNA COVID-19 Vaccines

CDC Interim Recommendations for People Fully Vaccinated Against Coronavirus

Immunogenicity of the Ad26.COV2.S COVID-19 Vaccine

Immunogenicity of a Single Dose of SARS-CoV-2 mRNA Vaccine in Solid Organ Transplant Recipients

Incentivizing Vaccination Uptake: The “Green Pass” Proposal in Israel

Adverse Reactions in the US to mRNA-Based Coronavirus Vaccines

Experts Discuss COVID-19—Variants and Vaccine Efficacy, Immunosuppressed Patients, and More

Asymptomatic and Symptomatic SARS-CoV-2 Infections After BNT162b2 Vaccination in a Routinely Screened Workforce

Effect of 2 Inactivated SARS-CoV-2 Vaccines on Symptomatic COVID-19 Infection in Adults

Restoring Vaccine Diplomacy in the Global COVID-19 Pandemic

One Year of COVID-19 Vaccines: A Shot of Hope, a Dose of Reality

See More

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