Abstract

The newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron sublineages, including the BA.2-derived BA.2.75.2 and the BA.5-derived BQ.1.1 and XBB.1, have accumulated additional spike mutations that may affect vaccine effectiveness. Here we report neutralizing activities of three human serum panels collected from individuals 23–94 days after dose 4 of a parental mRNA vaccine; 14–32 days after a BA.5 bivalent booster from individuals with 2–4 previous doses of parental mRNA vaccine; or 14–32 days after a BA.5 bivalent booster from individuals with previous SARS-CoV-2 infection and 2–4 doses of parental mRNA vaccine. The results showed that a BA.5 bivalent booster elicited a high neutralizing titer against BA.4/5 measured at 14–32 days after boost; however, the BA.5 bivalent booster did not produce robust neutralization against the newly emerged BA.2.75.2, BQ.1.1 or XBB.1. Previous infection substantially enhanced the magnitude and breadth of BA.5 bivalent booster-elicited neutralization. Our data support a vaccine update strategy that future boosters should match newly emerged circulating SARS-CoV-2 variants. Circulating variants of SARS-CoV-2 continue to evade neutralization by COVID-19 vaccines, including bivalent boosters that target the BA.4/BA.5 variants of concern, suggesting that strategies to get ahead of the virus’ evolution might be warranted.