Evolving antibody evasion and receptor affinity of the Omicron BA.2.75 sublineage of SARS-CoV-2

SARS-CoV-2 Omicron BA.2.75 has diversified into multiple subvariants with additional spike mutations, and several are expanding in prevalence, particularly CH.1.1 and BN.1. Here, we investigated the viral receptor affinities and neutralization evasion properties of major BA.2.75 subvariants actively circulating in different regions worldwide. We found two distinct evolutionary pathways and three newly identified mutations that shaped the virological features of these subvariants. One phenotypic group exhibited a discernible decrease in viral receptor affinities, but a noteworthy increase in resistance to antibody neutralization, as exemplified by CH.1.1, which is apparently as resistant as XBB.1.5. In contrast, a second group demonstrated a substantial increase in viral receptor affinity but only a moderate increase in antibody evasion, as exemplified by BN.1. We also observed that all prevalent SARS-CoV-2 variants in the circulation presently, except for BN.1, exhibit profound levels of antibody evasion, suggesting this is the dominant determinant of virus transmissibility today. ### Competing Interest Statement S.I, J.Y., 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. Aubree Gordon serves on a scientific advisory board for Janssen Pharmaceuticals. Other authors declare no competing interests.