PT - JOURNAL ARTICLE AU - Qian Wang AU - Sho Iketani AU - Zhiteng Li AU - Yicheng Guo AU - Andre Yanchen Yeh AU - Michael Liu AU - Jian Yu AU - Zizhang Sheng AU - Yaoxing Huang AU - Lihong Liu AU - David D. Ho TI - Antigenic characterization of the SARS-CoV-2 Omicron subvariant BA.2.75 AID - 10.1101/2022.07.31.502235 DP - 2022 Jan 01 TA - bioRxiv PG - 2022.07.31.502235 4099 - http://biorxiv.org/content/early/2022/08/01/2022.07.31.502235.short 4100 - http://biorxiv.org/content/early/2022/08/01/2022.07.31.502235.full AB - The SARS-CoV-2 Omicron subvariant BA.2.75 emerged recently and appears to be spreading rapidly. It has nine mutations in its spike compared to BA.2, raising concerns it may further evade vaccine-elicited and therapeutic antibodies. Here, we found BA.2.75 to be moderately more neutralization resistant to sera from vaccinated/boosted individuals than BA.2 (1.8-fold), similar to BA.2.12.1 (1.1-fold), but more neutralization sensitive than BA.4/5 (0.6-fold). Relative to BA.2, BA.2.75 showed heightened resistance to class 1 and class 3 monoclonal antibodies to the receptor-binding domain, while gaining sensitivity to class 2 antibodies. The resistance was largely conferred by the G446S and R460K mutations. Of note, BA.2.75 was slightly resistant (3.7-fold) to bebtelovimab, the only therapeutic antibody with potent activity against all Omicron subvariants. BA.2.75 also exhibited higher receptor binding affinity than other Omicron subvariants. BA.2.75 provides yet another example of the ongoing evolution of SARS-CoV-2 as it gains transmissibility while incrementally evading antibody neutralization.Competing Interest StatementS.I, J.Y., Y.H., L.L., and D.D.H. are inventors on patent applications (WO2021236998) or provisional patent applications (63/271,627) filed by Columbia University for a number of SARS-CoV-2 neutralizing antibodies described in this manuscript. Both sets of applications are under review. D.D.H. is a co-founder of TaiMed Biologics and RenBio, consultant to WuXi Biologics and Brii Biosciences, and board director for Vicarious Surgical.