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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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Corresponding Author: C. Buddy Creech MD, MPH, Division of Infectious Diseases, Vanderbilt University School of Medicine, D-7235 MCN, Nashville, TN 37232-2581 (firstname.lastname@example.org).
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.
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