Potent neutralizing antibodies directed to multiple epitopes on SARS-CoV-2 spike

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Here we report the isolation of 61 SARS-CoV-2-neutralizing monoclonal antibodies from 5 infected patients hospitalized with severe disease. Among these are 19 antibodies that potently neutralized the authentic SARS-CoV-2 in vitro, 9 of which exhibited exquisite potency, with 50% virus-inhibitory concentrations of 0.7 to 9 ng/mL.

https://www.nature.com/articles/s41586-020-2571-7

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Potent neutralizing antibodies directed to 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 & 
• David D. Ho 

Author information

Author notes

1. These authors contributed equally: Lihong Liu, Pengfei Wang, Manoj S. Nair, Jian Yu, Micah Rapp, Qian Wang

Affiliations

1. Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, 10032, USA

   Lihong Liu, Pengfei Wang, Manoj S. Nair, Jian Yu, Yang Luo, Vincent Sahi, Zizhang Sheng, Yaoxing Huang, Lawrence Shapiro & David D. Ho

2. Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY, 10027, USA

   Micah Rapp, Gabriele Cerutti, Jude Bimela, Zizhang Sheng & Lawrence Shapiro

3. Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, 02215, USA

   Qian Wang & Joseph G. Sodroski

4. State Key Laboratory of Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China

   Jasper F-W. Chan, Zhiwei Chen & Kwok-Yung Yuen

5. Centre for Virology, Vaccinology and Therapeutics, Health@InnoHK, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China

   Jasper F-W. Chan, Zhiwei Chen & Kwok-Yung Yuen

6. Department of Microbiology & Immunology Flow Cytometry Core, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, 10032, USA

   Amir Figueroa

7. Human Immune Monitoring Core, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, 10032, USA

   Xinzheng V. Guo

8. Vaccine Research Center, National Institutes of Health, Bethesda, MD, 20892, USA

   Jason Gorman, Tongqing Zhou & Peter D. Kwong

9. AIDS Institute, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China

   Zhiwei Chen

10. Department of Biochemistry, Columbia University, New York, NY, 10032, USA

    Peter D. Kwong & Lawrence Shapiro

11. Division of Infectious Diseases, Department of Internal Medicine, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, 10032, USA

    Michael T. Yin

Corresponding authors

Correspondence to Yaoxing Huang or Lawrence Shapiro or David D. Ho.

• Article
• Published: 22 July 2020

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Cite this article

Liu, L., Wang, P., Nair, M.S. et al. Potent neutralizing antibodies directed to multiple epitopes on SARS-CoV-2 spike. Nature (2020). https://doi.org/10.1038/s41586-020-2571-7

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• Received15 June 2020

• Accepted15 July 2020

• Published22 July 2020

• DOIhttps://doi.org/10.1038/s41586-020-2571-7

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Edited July 23, 2020 by niman

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Abstract

The SARS-CoV-2 pandemic rages on with devasting consequences on human lives and the global economy^1,2. The discovery and development of virus-neutralizing monoclonal antibodies could be one approach to treat or prevent infection by this novel coronavirus. Here we report the isolation of 61 SARS-CoV-2-neutralizing monoclonal antibodies from 5 infected patients hospitalized with severe disease. Among these are 19 antibodies that potently neutralized the authentic SARS-CoV-2 in vitro, 9 of which exhibited exquisite potency, with 50% virus-inhibitory concentrations of 0.7 to 9 ng/mL. Epitope mapping showed this collection of 19 antibodies to be about equally divided between those directed to the receptor-binding domain (RBD) and those to 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 targeting RBD, a second targeting NTD, and a third bridging two separate RBDs revealed recognition of 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.