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This article reviews strategies for vaccine development and distribution to combat the COVID-19 pandemic. Once the viral spike protein was identified as a target, several strategies were attempted to induce a protective immune response. These include chemically inactivated virus grown in culture, recombinant protein subunits, or viral vectors containing genetic sequence corresponding to the target antigen. Each of these mechanisms of vaccination has specific challenges, but viral vectors with spike protein mRNA have been developed by Pfizer-BioNTech and Moderna with >90% efficacy against clinical disease from SARS-CoV-2.
Important public health considerations have affected vaccine distribution, which will be an important step towards controlling this pandemic.
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 SARSCoV-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