Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the identified cause of coronavirus disease 2019 (COVID-19), continues unabated. This fact, coupled with recurrence of COVID-19 in areas where it had been controlled, highlights the critical need for a safe and effective vaccine to prevent and mitigate this novel virus. The spike protein of SARS-CoV-2 is important in its lifecycle as well as in the development of immunity after human infection. This has prompted the selection of this antigen as a focus in developing COVID-19 vaccines. This article provides (1) a summary of the host immune responses to SARS-CoV-2 infection, (2) the vaccine platforms being used with COVID-19 vaccine candidates undergoing, or about to undergo, Phase III clinical trial testing, and (3) an overview of the key criteria necessary for COVID-19 vaccine efficacy and safety. In addition, the unique concept of vaccine-enhanced disease will be discussed. [Pediatr Ann. 2020;49(12):e532-e536.].
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