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Potent neutralizing antibodies against multiple epitopes on SARS-CoV-2 spike.
Nature. 2020 08; 584(7821):450-456.Nat

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.

Authors+Show Affiliations

Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA.Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA.Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA.Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA.Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY, USA.Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA.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. Centre for Virology, Vaccinology and Therapeutics, Health@InnoHK, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA.Department of Microbiology & Immunology Flow Cytometry Core, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA.Human Immune Monitoring Core, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA.Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY, USA.Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY, USA.Vaccine Research Center, National Institutes of Health, Bethesda, MD, USA.Vaccine Research Center, National Institutes of Health, Bethesda, MD, USA.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. Centre for Virology, Vaccinology and Therapeutics, Health@InnoHK, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China. AIDS Institute, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.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. Centre for Virology, Vaccinology and Therapeutics, Health@InnoHK, The University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, China.Vaccine Research Center, National Institutes of Health, Bethesda, MD, USA. Department of Biochemistry, Columbia University, New York, NY, USA.Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.Division of Infectious Diseases, Department of Internal Medicine, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA.Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA. Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY, USA.Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA. yh3253@cumc.columbia.edu.Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA. lss8@columbia.edu. Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY, USA. lss8@columbia.edu. Department of Biochemistry, Columbia University, New York, NY, USA. lss8@columbia.edu.Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA. dh2994@cumc.columbia.edu.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32698192

Citation

Liu, Lihong, et al. "Potent Neutralizing Antibodies Against Multiple Epitopes On SARS-CoV-2 Spike." Nature, vol. 584, no. 7821, 2020, pp. 450-456.
Liu L, Wang P, Nair MS, et al. Potent neutralizing antibodies against multiple epitopes on SARS-CoV-2 spike. Nature. 2020;584(7821):450-456.
Liu, L., Wang, P., Nair, M. S., Yu, J., Rapp, M., Wang, Q., Luo, Y., Chan, J. F., Sahi, V., Figueroa, A., Guo, X. V., Cerutti, G., Bimela, J., Gorman, J., Zhou, T., Chen, Z., Yuen, K. Y., Kwong, P. D., Sodroski, J. G., ... Ho, D. D. (2020). Potent neutralizing antibodies against multiple epitopes on SARS-CoV-2 spike. Nature, 584(7821), 450-456. https://doi.org/10.1038/s41586-020-2571-7
Liu L, et al. Potent Neutralizing Antibodies Against Multiple Epitopes On SARS-CoV-2 Spike. Nature. 2020;584(7821):450-456. PubMed PMID: 32698192.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Potent neutralizing antibodies against multiple epitopes on SARS-CoV-2 spike. AU - Liu,Lihong, AU - Wang,Pengfei, AU - Nair,Manoj S, AU - Yu,Jian, AU - Rapp,Micah, AU - Wang,Qian, AU - Luo,Yang, AU - Chan,Jasper F-W, AU - Sahi,Vincent, AU - Figueroa,Amir, AU - Guo,Xinzheng V, AU - Cerutti,Gabriele, AU - Bimela,Jude, AU - Gorman,Jason, AU - Zhou,Tongqing, AU - Chen,Zhiwei, AU - Yuen,Kwok-Yung, AU - Kwong,Peter D, AU - Sodroski,Joseph G, AU - Yin,Michael T, AU - Sheng,Zizhang, AU - Huang,Yaoxing, AU - Shapiro,Lawrence, AU - Ho,David D, Y1 - 2020/07/22/ PY - 2020/06/15/received PY - 2020/07/15/accepted PY - 2020/7/23/pubmed PY - 2020/8/28/medline PY - 2020/7/23/entrez SP - 450 EP - 456 JF - Nature JO - Nature VL - 584 IS - 7821 N2 - 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. SN - 1476-4687 UR - https://www.unboundmedicine.com/medline/citation/32698192/Potent_neutralizing_antibodies_against_multiple_epitopes_on_SARS_CoV_2_spike_ L2 - https://doi.org/10.1038/s41586-020-2571-7 DB - PRIME DP - Unbound Medicine ER -