Cell Reports (May 2023)
Fortuitous somatic mutations during antibody evolution endow broad neutralization against SARS-CoV-2 Omicron variants
- Jianbo Wu,
- Zhenguo Chen,
- Yidan Gao,
- Zegen Wang,
- Jiarong Wang,
- Bing-Yu Chiang,
- Yunjiao Zhou,
- Yuru Han,
- Wuqiang Zhan,
- Minxiang Xie,
- Weiyu Jiang,
- Xiang Zhang,
- Aihua Hao,
- Anqi Xia,
- Jiaying He,
- Song Xue,
- Christian T. Mayer,
- Fan Wu,
- Bin Wang,
- Lunan Zhang,
- Lei Sun,
- Qiao Wang
Affiliations
- Jianbo Wu
- 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 Sciences, School of Public Health, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China
- Zhenguo Chen
- 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 Sciences, School of Public Health, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China
- Yidan Gao
- 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 Sciences, School of Public Health, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China
- Zegen Wang
- Advaccine Biopharmaceuticals Suzhou Co., Ltd., Suzhou, China
- Jiarong Wang
- Advaccine Biopharmaceuticals Suzhou Co., Ltd., Suzhou, China
- Bing-Yu Chiang
- Advaccine Biopharmaceuticals Suzhou Co., Ltd., Suzhou, China
- Yunjiao Zhou
- Fundamental Research Center, Shanghai Yangzhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), School of Medicine, Tongji University, Shanghai 201619, China
- Yuru Han
- 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 Sciences, School of Public Health, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China
- Wuqiang Zhan
- 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 Sciences, School of Public Health, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China
- Minxiang Xie
- 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 Sciences, School of Public Health, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China
- Weiyu Jiang
- 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 Sciences, School of Public Health, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China
- Xiang Zhang
- 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 Sciences, School of Public Health, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China
- Aihua Hao
- 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 Sciences, School of Public Health, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China
- Anqi Xia
- 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 Sciences, School of Public Health, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China
- Jiaying He
- 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 Sciences, School of Public Health, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China
- Song Xue
- 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 Sciences, School of Public Health, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China
- Christian T. Mayer
- Experimental Immunology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
- Fan Wu
- 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 Sciences, School of Public Health, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China
- Bin Wang
- 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 Sciences, School of Public Health, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China; Advaccine Biopharmaceuticals Suzhou Co., Ltd., Suzhou, China
- Lunan Zhang
- 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 Sciences, School of Public Health, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China; Advaccine Biopharmaceuticals Suzhou Co., Ltd., Suzhou, China; Corresponding author
- Lei Sun
- 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 Sciences, School of Public Health, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China; Corresponding author
- Qiao Wang
- 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 Sciences, School of Public Health, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China; Corresponding author
- Journal volume & issue
-
Vol. 42,
no. 5
p. 112503
Abstract
Summary: 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.
