<h4>Background</h4>Emergence of severe acute respiratory syndrome coronavirus 2 sublineages warrants the use of sequence-adapted vaccines to provide protection against coronavirus disease 2019.<h4>Methods</h4>In this phase 3 trial, adults 18‒55 years old who had previously received three 30 μg doses of BNT162b2 vaccine were randomized to receive a 60 or 30 μg dose of bivalent Omicron BA.1‒adapted BNT162b2 comprising equal amounts of ancestral and monovalent messenger RNA BA.1 (bivalent BA.1) or a 60 μg dose of monovalent Omicron BA.1‒adapted BNT162b2 (monovalent BA.1). This evidence concerns the gene CFB and COVID-19.