bioRxiv : the preprint server for biology · 2022
Fortuitous Somatic Mutations during Antibody Evolution Endow Broad Neutralization against SARS-CoV-2 Omicron Variants.
ПрепринтСтатьяНазвание и аннотация: Перевод в очереди
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Wu Jianbo, Chen Zhenguo, Gao Yidan, Wang Zegen, Wang Jiarong, Chiang Bing-Yu, Zhou Yunjiao, Han Yuru, Zhan Wuqiang, Xie Minxiang, Jiang Weiyu, Zhang Xiang, Hao Aihua, Xia Anqi, He Jiaying, Xue Song, Mayer Christian T, Wu Fan, Wang Bin, Zhang Lunan, Sun Lei, Wang Qiao
Аннотация
Striking antibody evasion by emerging circulating SARS-CoV-2 variants drives the identification of broadly neutralizing antibodies (bNAbs). However, how a bNAb acquires increased neutralization breadth during antibody evolution is still elusive. Here, we identified a clonally-related antibody family from a convalescent individual. One of the members, XG005, exhibited potent and broad neutralizing activities against SARS-CoV-2 variants, while the other members showed significant reductions in neutralization breadth and potency, especially against the Omicron sublineages. Structural analysis visualizing the XG005-Omicron spike binding interface revealed how crucial somatic mutations endowed XG005 with greater neutralization potency and breadth. A single administration of XG005 with extended half-life, reduced antibody-dependent enhancement (ADE) effect, and increased antibody product quality, exhibited a high therapeutic efficacy in BA.2- and BA.5-challenged mice. Our results provided a natural example to show the importance of somatic hypermutation during antibody evolution for SARS-CoV-2 neutralization breadth and potency.