niman Posted July 23, 2020 Report Share Posted July 23, 2020 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 Link to comment Share on other sites More sharing options...
niman Posted July 23, 2020 Author Report Share Posted July 23, 2020 (edited) 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 These authors contributed equally: Lihong Liu, Pengfei Wang, Manoj S. Nair, Jian Yu, Micah Rapp, Qian Wang Affiliations 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 Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY, 10027, USA Micah Rapp, Gabriele Cerutti, Jude Bimela, Zizhang Sheng & Lawrence Shapiro Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, 02215, USA Qian Wang & Joseph G. Sodroski 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 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 Department of Microbiology & Immunology Flow Cytometry Core, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, 10032, USA Amir Figueroa Human Immune Monitoring Core, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, 10032, USA Xinzheng V. Guo Vaccine Research Center, National Institutes of Health, Bethesda, MD, 20892, USA Jason Gorman, Tongqing Zhou & Peter D. Kwong AIDS Institute, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China Zhiwei Chen Department of Biochemistry, Columbia University, New York, NY, 10032, USA Peter D. Kwong & Lawrence Shapiro 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 This is an unedited manuscript that has been accepted for publication. Nature Research are providing this early version of the manuscript as a service to our authors and readers. The manuscript will undergo copyediting, typesetting and a proof review before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers apply. 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 Download citation Received15 June 2020 Accepted15 July 2020 Published22 July 2020 DOIhttps://doi.org/10.1038/s41586-020-2571-7 https://rdcu.be/b5MEB Edited July 23, 2020 by niman Link to comment Share on other sites More sharing options...
niman Posted July 23, 2020 Author Report Share Posted July 23, 2020 Abstract The SARS-CoV-2 pandemic rages on with devasting consequences on 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 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. Link to comment Share on other sites More sharing options...
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