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

Lihong Liu, Pengfei Wang, Manoj S. Nair, Jian Yu, Micah Rapp, Qian Wang, Yang Luo, Jasper F.-W. Chan, Vincent Sahi, Amir Figueroa, Xinzheng V. Guo, Gabriele Cerutti, Jude Bimela, Jason Gorman, Tongqing Zhou, Zhiwei Chen, Kwok-Yung Yuen, Peter D. Kwong, Joseph G. Sodroski, Michael T. Yin, Zizhang Sheng, Yaoxing Huang (), Lawrence Shapiro () and David D. Ho ()
Additional contact information
Lihong Liu: Columbia University Vagelos College of Physicians and Surgeons
Pengfei Wang: Columbia University Vagelos College of Physicians and Surgeons
Manoj S. Nair: Columbia University Vagelos College of Physicians and Surgeons
Jian Yu: Columbia University Vagelos College of Physicians and Surgeons
Micah Rapp: Columbia University
Qian Wang: Harvard Medical School
Yang Luo: Columbia University Vagelos College of Physicians and Surgeons
Jasper F.-W. Chan: The University of Hong Kong, Hong Kong Special Administrative Region
Vincent Sahi: Columbia University Vagelos College of Physicians and Surgeons
Amir Figueroa: Columbia University Vagelos College of Physicians and Surgeons
Xinzheng V. Guo: Columbia University Vagelos College of Physicians and Surgeons
Gabriele Cerutti: Columbia University
Jude Bimela: Columbia University
Jason Gorman: National Institutes of Health
Tongqing Zhou: National Institutes of Health
Zhiwei Chen: The University of Hong Kong, Hong Kong Special Administrative Region
Kwok-Yung Yuen: The University of Hong Kong, Hong Kong Special Administrative Region
Peter D. Kwong: National Institutes of Health
Joseph G. Sodroski: Harvard Medical School
Michael T. Yin: Columbia University Vagelos College of Physicians and Surgeons
Zizhang Sheng: Columbia University Vagelos College of Physicians and Surgeons
Yaoxing Huang: Columbia University Vagelos College of Physicians and Surgeons
Lawrence Shapiro: Columbia University Vagelos College of Physicians and Surgeons
David D. Ho: Columbia University Vagelos College of Physicians and Surgeons

Nature, 2020, vol. 584, issue 7821, 450-456

Abstract: Abstract 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.

Date: 2020
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DOI: 10.1038/s41586-020-2571-7

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