Identification of a highly conserved neutralizing epitope within the RBD region of diverse SARS-CoV-2 variants
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Published:2024-01-29
Issue:1
Volume:15
Page:
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ISSN:2041-1723
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Container-title:Nature Communications
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language:en
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Short-container-title:Nat Commun
Author:
Wang YanqunORCID, Yan An, Song DeyongORCID, Duan Maoqin, Dong Chuangchuang, Chen Jiantao, Jiang Zihe, Gao Yuanzhu, Rao Muding, Feng Jianxia, Zhang Zhaoyong, Qi Ruxi, Ma XiaominORCID, Liu Hong, Yu Beibei, Wang Qiaoping, Zong Mengqi, Jiao Jie, Xing Pingping, Pan Rongrong, Li Dan, Xiao Juxue, Sun Junbo, Li Ying, Zhang Linfeng, Shen Zhenduo, Sun Baiping, Zhao Yanyan, Zhang Lu, Dai Jun, Zhao JingxianORCID, Wang LanORCID, Dou Changlin, Liu ZhengORCID, Zhao JincunORCID
Abstract
AbstractThe constant emergence of SARS-CoV-2 variants continues to impair the efficacy of existing neutralizing antibodies, especially XBB.1.5 and EG.5, which showed exceptional immune evasion properties. Here, we identify a highly conserved neutralizing epitope targeted by a broad-spectrum neutralizing antibody BA7535, which demonstrates high neutralization potency against not only previous variants, such as Alpha, Beta, Gamma, Delta and Omicron BA.1-BA.5, but also more recently emerged Omicron subvariants, including BF.7, CH.1.1, XBB.1, XBB.1.5, XBB.1.9.1, EG.5. Structural analysis of the Omicron Spike trimer with BA7535-Fab using cryo-EM indicates that BA7535 recognizes a highly conserved cryptic receptor-binding domain (RBD) epitope, avoiding most of the mutational hot spots in RBD. Furthermore, structural simulation based on the interaction of BA7535-Fab/RBD complexes dissects the broadly neutralizing effect of BA7535 against latest variants. Therapeutic and prophylactic treatment with BA7535 alone or in combination with BA7208 protected female mice from the circulating Omicron BA.5 and XBB.1 variant infection, suggesting the highly conserved neutralizing epitope serves as a potential target for developing highly potent therapeutic antibodies and vaccines.
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary
Reference54 articles.
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