Improved Neutralization of Omicron BA.4/5, BA.4.6, BA.2.75.2, BQ.1.1, and XBB.1 with Bivalent BA.4/5 Vaccine

The BNT162b2 bivalent BA.4/5 COVID-19 vaccine has been authorized to mitigate COVID-19 due to current Omicron and potentially future variants. New sublineages of SARS-CoV-2 Omicron continue to emerge and have acquired additional mutations, particularly in the spike protein, that may lead to improved viral fitness and immune evasion. The present study characterized neutralization activities against new Omicron sublineages BA.4.6, BA.2.75.2, BQ.1.1, and XBB.1 after a 4th dose (following three doses of BNT162b2) of either the original monovalent BNT162b2 or the bivalent BA.4/5 booster in individuals >55 years of age. For all participants, the 4th dose of monovalent BNT162b2 vaccine induced a 3.0, 2.9, 2.3, 2.1, 1.8, and 1.5 geometric mean neutralizing titer fold rise (GMFR) against USA/WA1-2020 (a strain isolated in January 2020), BA.4/5, BA.4.6, BA.2.75.2, BQ.1.1, and XBB.1, respectively; the bivalent vaccine induced 5.8, 13.0, 11.1, 6.7, 8.7, and 4.8 GMFRs. For individuals without SARS-CoV-2 infection history, BNT162b2 monovalent induced 4.4, 3.0, 2.5, 2.0, 1.5, and 1.3 GMFRs, respectively; the bivalent vaccine induced 9.9, 26.4, 22.2, 8.4, 12.6, and 4.7 GMFRs. These data suggest the bivalent BA.4/5 vaccine is more immunogenic than the original BNT162b2 monovalent vaccine against circulating Omicron sublineages, including BQ.1.1 that is becoming prevalent globally. ### Competing Interest Statement X.X. and P.-Y.S. have filed a patent on the reverse genetic system of SARS-CoV-2. J.Z., C.K., X.X., and P.-Y.S. received compensation from Pfizer to perform the project. A.S.A.,Q.Y., H.C., M.C., D.C., N.K., S.P., K.T., K.A.S., Y.Z., D-Y.L., and W.C.G. are employees of Pfizer and may hold stock options. A.M. and U.S. are employees of BioNTech and may hold stock options.