Additional mutations based on Omicron BA.2.75 mediate its further evasion from broadly neutralizing antibodies

Huimin Guo; Jie Jiang; Senlin Shen; Xiangyang Ge; Qing Fan; Bing Zhou; Lin Cheng; Bin Ju; Zheng Zhang

doi:10.1016/j.isci.2023.106283

Additional mutations based on Omicron BA.2.75 mediate its further evasion from broadly neutralizing antibodies

iScience. 2023 Apr 21;26(4):106283. doi: 10.1016/j.isci.2023.106283. Epub 2023 Feb 27.

Authors

Huimin Guo¹, Jie Jiang¹, Senlin Shen¹, Xiangyang Ge¹, Qing Fan¹, Bing Zhou¹, Lin Cheng¹, Bin Ju^{1

2}, Zheng Zhang^{1

2

3}

Affiliations

¹ Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital, The Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong Province 518112, China.
² Guangdong Key Laboratory for Anti-infection Drug Quality Evaluation, Shenzhen, Guangdong Province 518112, China.
³ Shenzhen Research Center for Communicable Disease Diagnosis and Treatment of Chinese Academy of Medical Science, Shenzhen, Guangdong Province 518112, China.

Abstract

SARS-CoV-2 Omicron BA.2.75 subvariant has evolved to a series of progeny variants carrying several additional mutations in the receptor-binding domain (RBD). Here, we investigated whether and how these single mutations based on BA.2.75 affect the neutralization of currently available anti-RBD monoclonal antibodies (mAbs) with well-defined structural information. Approximately 34% of mAbs maintained effective neutralizing activities against BA.2.75, consistent with those against BA.2, BA.4/5, and BA.2.12.1. Single additional R346T, K356T, L452R, or F486S mutations further facilitated BA.2.75-related progeny variants to escape from broadly neutralizing antibodies (bnAbs) at different degree. Only LY-CoV1404 (bebtelovimab) displayed a first-class neutralization potency and breadth against all tested Omicron subvariants. Overall, these data make a clear connection between virus escape and antibody recognizing antigenic epitopes, which facilitate to develop next-generation universal bnAbs against emerging SARS-CoV-2 variants.

Keywords: Immunology; Virology.