Antigenic characterization of the SARS-CoV-2 Omicron subvariant BA.2.75

作者：Qian Wang, Sho Iketani, Zhiteng Li, Yicheng Guo, Andre Yanchen Yeh, Michael Liu, Jian Yu, Zizhang Sheng, Yaoxing Huang, Lihong Liu, David D. Ho · 发表于：Cell Host & Microbe · 年份：2022 · DOI：10.1016/j.chom.2022.09.002 · 被引用次数：123 · 研究领域：SARS-CoV-2 and COVID-19 Research、COVID-19 Clinical Research Studies、SARS-CoV-2 detection and testing

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariant BA.2.75 emerged recently and appears to be spreading. It has nine mutations in spike compared with the currently circulating BA.2, raising concerns that it may further evade vaccine-elicited and therapeutic antibodies. 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 targeting the spike-receptor-binding domain while gaining sensitivity to class 2 antibodies. Resistance was largely conferred by G446S and R460K mutations. BA.2.75 was slightly resistant (3.7-fold) to bebtelovimab, a therapeutic antibody with potent activity against all Omicron subvariants. BA.2.75 also exhibited a higher binding affinity to host receptor ACE2 than other Omicron subvariants. BA.2.75 provides further insight into SARS-CoV-2 evolution as it gains transmissibility while incrementally evading antibody neutralization.