Maqola

Potent neutralizing antibodies against multiple epitopes on SARS-CoV-2 spike

Lihong LiuAaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USAPengfei WangAaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USAManoj S. NairAaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USAJian YuAaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USAMicah RappZuckerman Mind Brain Behavior Institute, Columbia University, New York, NY, USAQian WangDana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USAYang LuoAaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USAJasper Fuk‐Woo ChanCentre for Virology, Vaccinology and Therapeutics, Health@InnoHK, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, ChinaVincent SahiAaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USAAmir FigueroaDepartment of Microbiology & Immunology Flow Cytometry Core, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USAXinzheng V. GuoHuman Immune Monitoring Core, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USAGabriele CeruttiZuckerman Mind Brain Behavior Institute, Columbia University, New York, NY, USAJude BimelaZuckerman Mind Brain Behavior Institute, Columbia University, New York, NY, USAJason GormanVaccine Research Center, National Institutes of Health, Bethesda, MD, USATongqing ZhouVaccine Research Center, National Institutes of Health, Bethesda, MD, USAZhiwei ChenAIDS Institute, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, ChinaKwok‐Yung YuenCentre for Virology, Vaccinology and Therapeutics, Health@InnoHK, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, ChinaPeter D. KwongDepartment of Biochemistry, Columbia University, New York, NY, USAJoseph SodroskiDana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USAMichael T. YinDivision of Infectious Diseases, Department of Internal Medicine, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USAZizhang ShengAaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USAYaoxing HuangAaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA. [email protected]Lawrence ShapiroAaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA. [email protected]David D. HoAaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA. [email protected]

2020en

ABI

Annotatsiya

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic continues, with devasting consequences for human lives and the global economy1,2. The discovery and development of virus-neutralizing monoclonal antibodies could be one approach to treat or prevent infection by this coronavirus. Here we report the isolation of sixty-one SARS-CoV-2-neutralizing monoclonal antibodies from five patients infected with SARS-CoV-2 and admitted to hospital with severe coronavirus disease 2019 (COVID-19). Among these are nineteen antibodies that potently neutralized authentic SARS-CoV-2 in vitro, nine of which exhibited very high potency, with 50% virus-inhibitory concentrations of 0.7 to 9 ng ml−1. Epitope mapping showed that this collection of nineteen antibodies was about equally divided between those directed against the receptor-binding domain (RBD) and those directed against the N-terminal domain (NTD), indicating that both of these regions at the top of the viral spike are immunogenic. In addition, two other powerful neutralizing antibodies recognized quaternary epitopes that overlap with the domains at the top of the spike. Cryo-electron microscopy reconstructions of one antibody that targets the RBD, a second that targets the NTD, and a third that bridges two separate RBDs showed that the antibodies recognize the closed, ‘all RBD-down’ conformation of the spike. Several of these monoclonal antibodies are promising candidates for clinical development as potential therapeutic and/or prophylactic agents against SARS-CoV-2. A diverse collection of potent neutralizing antibodies against the SARS-CoV-2 spike protein have been isolated from five patients with severe COVID-19 and high serum neutralization titres.

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DOI: 10.1038/s41586-020-2571-7

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