PT  - JOURNAL ARTICLE
AU  - Yunlong Cao
AU  - Weiliang Song
AU  - Lei Wang
AU  - Pan Liu
AU  - Can Yue
AU  - Fanchong Jian
AU  - Yuanling Yu
AU  - Ayijiang Yisimayi
AU  - Peng Wang
AU  - Yao Wang
AU  - Qianhui Zhu
AU  - Jie Deng
AU  - Wangjun Fu
AU  - Lingling Yu
AU  - Na Zhang
AU  - Jing Wang
AU  - Tianhe Xiao
AU  - Ran An
AU  - Jing Wang
AU  - Lu Liu
AU  - Sijie Yang
AU  - Xiao Niu
AU  - Qingqing Gu
AU  - Fei Shao
AU  - Xiaohua Hao
AU  - Ronghua Jin
AU  - Youchun Wang
AU  - Xiaoliang Sunney Xie
AU  - Xiangxi Wang
TI  - Characterizations of enhanced infectivity and antibody evasion of Omicron BA.2.75
AID  - 10.1101/2022.07.18.500332
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.07.18.500332
4099  - http://biorxiv.org/content/early/2022/08/10/2022.07.18.500332.short
4100  - http://biorxiv.org/content/early/2022/08/10/2022.07.18.500332.full
AB  - Recently emerged SARS-CoV-2 Omicron subvariant, BA.2.75, displayed a local growth advantage over BA.2.38, BA.2.76 and BA.5 in India. The underlying mechanism of BA.2.75’s enhanced infectivity, especially compared to BA.5, remains unclear. Here, we show that BA.2.75 exhibits substantially higher ACE2-binding affinity than BA.5. Also, BA.2.75 spike shows decreased thermostability and increased “up” RBD conformation in acidic conditions, suggesting enhanced low-pH-endosomal cell-entry pathway utilization. BA.2.75 is less humoral immune evasive than BA.4/BA.5 in BA.1/BA.2 breakthrough-infection convalescents; however, BA.2.75 shows heavier neutralization evasion in Delta breakthrough-infection convalescents. Importantly, plasma from BA.5 breakthrough infection exhibit significantly weaker neutralization against BA.2.75 than BA.5, mainly due to BA.2.75’s distinct RBD and NTD-targeting antibody escaping pattern from BA.4/BA.5. Additionally, Evusheld and Bebtelovimab remain effective against BA.2.75, and Sotrovimab recovered RBD-binding affinity. Together, our results suggest BA.2.75 may prevail after the global BA.4/BA.5 wave, and its increased receptor-binding capability could allow further incorporation of immune-evasive mutations.Competing Interest StatementX.S.X. and Y.C. are inventors on the provisional patent applications of BD series antibodies, which includes BD30-604 (DXP-604), BD55-5840 (SA58) and BD55-5514 (SA55). X.S.X. and Y.C. are founders of Singlomics Biopharmaceuticals. Other authors declare no competing interests.