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Fortuitous somatic mutations during antibody evolution endow broad neutralization against SARS-CoV-2 Omicron variants.
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.
  • Wu J; Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, Shanghai Fifth People's Hospital, Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sc
  • Chen Z; Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, Shanghai Fifth People's Hospital, Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sc
  • Gao Y; Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, Shanghai Fifth People's Hospital, Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sc
  • Wang Z; Advaccine Biopharmaceuticals Suzhou Co., Ltd., Suzhou, China.
  • Wang J; Advaccine Biopharmaceuticals Suzhou Co., Ltd., Suzhou, China.
  • Chiang BY; Advaccine Biopharmaceuticals Suzhou Co., Ltd., Suzhou, China.
  • Zhou Y; Fundamental Research Center, Shanghai Yangzhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), School of Medicine, Tongji University, Shanghai 201619, China.
  • Han Y; Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, Shanghai Fifth People's Hospital, Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sc
  • Zhan W; Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, Shanghai Fifth People's Hospital, Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sc
  • Xie M; Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, Shanghai Fifth People's Hospital, Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sc
  • Jiang W; Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, Shanghai Fifth People's Hospital, Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sc
  • Zhang X; Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, Shanghai Fifth People's Hospital, Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sc
  • Hao A; Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, Shanghai Fifth People's Hospital, Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sc
  • Xia A; Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, Shanghai Fifth People's Hospital, Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sc
  • He J; Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, Shanghai Fifth People's Hospital, Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sc
  • Xue S; Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, Shanghai Fifth People's Hospital, Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sc
  • Mayer CT; Experimental Immunology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
  • Wu F; Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, Shanghai Fifth People's Hospital, Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sc
  • Wang B; Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, Shanghai Fifth People's Hospital, Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sc
  • Zhang L; Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, Shanghai Fifth People's Hospital, Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sc
  • Sun L; Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, Shanghai Fifth People's Hospital, Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sc
  • Wang Q; Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Institute of Infectious Disease and Biosecurity, Shanghai Frontiers Science Center of Pathogenic Microbes and Infection, Shanghai Fifth People's Hospital, Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sc
Cell Rep ; 42(5): 112503, 2023 05 30.
Article in English | MEDLINE | ID: covidwho-2311643
ABSTRACT
Striking antibody evasion by emerging circulating severe acute respiratory syndrome coronavirus 2 (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 identify a clonally related antibody family from a convalescent individual. One of the members, XG005, exhibits potent and broad neutralizing activities against SARS-CoV-2 variants, while the other members show significant reductions in neutralization breadth and potency, especially against the Omicron sublineages. Structural analysis visualizing the XG005-Omicron spike binding interface reveals how crucial somatic mutations endow 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 exhibits a high therapeutic efficacy in BA.2- and BA.5-challenged mice. Our results provide a natural example to show the importance of somatic hypermutation during antibody evolution for SARS-CoV-2 neutralization breadth and potency.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Type of study: Randomized controlled trials Topics: Variants Limits: Animals Language: English Journal: Cell Rep Year: 2023 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Type of study: Randomized controlled trials Topics: Variants Limits: Animals Language: English Journal: Cell Rep Year: 2023 Document Type: Article