Clinical development of variant-adapted BNT162b2 COVID-19 vaccines: the early Omicron era.

INTRODUCTION: The Omicron BA.1 variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and subsequent sub-lineages exhibit partial escape from neutralizing antibodies elicited by vaccines containing or encoding wild-type spike protein. In response to the emergence of Omicron sub-lineages, variant-adapted vaccines that contain or encode for Omicron spike protein components have been developed. AREAS COVERED: This review presents currently available clinical immunogenicity and safety data on Omicron variant-adapted versions of the BNT162b2 messenger RNA (mRNA) vaccine and summarizes the expected mechanism of action, and rationale for development, of these vaccines. In addition, challenges encountered during development and regulatory approval are discussed. EXPERT OPINION: Omicron-adapted BNT162b2 vaccines provide a wider breadth and potentially more durable protection against Omicron sub-lineages and antigenically aligned variants when compared with the original vaccine. As SARS-CoV-2 continues to evolve, further vaccine updates may be required. To facilitate this, a globally harmonized regulatory process for the transition to updated vaccines is needed. Next-generation vaccine approaches may provide broader protection against future variants.