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Rapid isolation and profiling of a diverse panel of human monoclonal antibodies targeting the SARS-CoV-2 spike protein

Seth J. Zost, Pavlo Gilchuk, Rita E. Chen, James Brett Case, Joseph X. Reidy, Andrew Trivette, Rachel S. Nargi, Rachel E. Sutton, Naveenchandra Suryadevara, Elaine C. Chen, Elad Binshtein, Swathi Shrihari, Mario Ostrowski, Helen Y. Chu, Jonathan E. Didier, Keith W. MacRenaris, Taylor Jones, Samuel Day, Luke Myers, F. Eun-Hyung Lee, Doan C. Nguyen, Ignacio Sanz, David R. Martinez, Ralph S. Baric, Larissa B. Thackray, Michael S. Diamond, View ORCID ProfileRobert H. Carnahan, James E. Crowe Jr.
doi: https://doi.org/10.1101/2020.05.12.091462
Seth J. Zost
1Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN, 37232, USA
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Pavlo Gilchuk
1Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN, 37232, USA
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Rita E. Chen
2Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO, 63110, USA
9Department of Medicine, Washington University School of Medicine, St. Louis, 63110, MO, USA
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James Brett Case
3Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, 37232, USA
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Joseph X. Reidy
1Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN, 37232, USA
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Andrew Trivette
1Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN, 37232, USA
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Rachel S. Nargi
1Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN, 37232, USA
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Rachel E. Sutton
1Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN, 37232, USA
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Naveenchandra Suryadevara
1Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN, 37232, USA
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Elaine C. Chen
3Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, 37232, USA
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Elad Binshtein
1Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN, 37232, USA
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Swathi Shrihari
9Department of Medicine, Washington University School of Medicine, St. Louis, 63110, MO, USA
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Mario Ostrowski
4Department of Medicine, University of Toronto, Toronto, ON, Canada
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Helen Y. Chu
5Division of Allergy and Infectious Diseases, University of Washington, Seattle 98109, USA
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Jonathan E. Didier
6Berkeley Lights, Inc., Emeryville, CA, 94608, USA
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Keith W. MacRenaris
6Berkeley Lights, Inc., Emeryville, CA, 94608, USA
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Taylor Jones
1Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN, 37232, USA
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Samuel Day
1Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN, 37232, USA
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Luke Myers
1Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN, 37232, USA
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F. Eun-Hyung Lee
7Department of Medicine, Emory University, Atlanta, GA, 30322 USA
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Doan C. Nguyen
7Department of Medicine, Emory University, Atlanta, GA, 30322 USA
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Ignacio Sanz
7Department of Medicine, Emory University, Atlanta, GA, 30322 USA
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David R. Martinez
8Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA
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Ralph S. Baric
8Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA
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Larissa B. Thackray
9Department of Medicine, Washington University School of Medicine, St. Louis, 63110, MO, USA
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Michael S. Diamond
2Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO, 63110, USA
9Department of Medicine, Washington University School of Medicine, St. Louis, 63110, MO, USA
10Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, 63110, USA
11Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO, 63110, USA
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Robert H. Carnahan
1Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN, 37232, USA
12Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, 37232, USA
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  • ORCID record for Robert H. Carnahan
  • For correspondence: james.crowe@vumc.org
James E. Crowe Jr.
1Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN, 37232, USA
3Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, 37232, USA
12Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, 37232, USA
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  • For correspondence: james.crowe@vumc.org
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Abstract

Antibodies are a principal determinant of immunity for most RNA viruses and have promise to reduce infection or disease during major epidemics. The novel coronavirus SARS-CoV-2 has caused a global pandemic with millions of infections and hundreds of thousands of deaths to date1,2. In response, we used a rapid antibody discovery platform to isolate hundreds of human monoclonal antibodies (mAbs) against the SARS-CoV-2 spike (S) protein. We stratify these mAbs into five major classes based on their reactivity to subdomains of S protein as well as their cross-reactivity to SARS-CoV. Many of these mAbs inhibit infection of authentic SARS-CoV-2 virus, with most neutralizing mAbs recognizing the receptor-binding domain (RBD) of S. This work defines sites of vulnerability on SARS-CoV-2 S and demonstrates the speed and robustness of new antibody discovery methodologies.

Competing Interest Statement

R.S.B. has served as a consultant for Takeda and Sanofi Pasteur on issues related to vaccines. M.S.D. is a consultant for Inbios Vir Biotechnology, NGM Biopharmaceuticals, Eli Lilly, and on the Scientific Advisory Board of Moderna, and a recipient of unrelated research grants from Moderna and Emergent BioSolutions. J.E.C. has served as a consultant for Sanofi and is on the Scientific Advisory Boards of CompuVax and Meissa Vaccines, is a recipient of previous unrelated research grants from Moderna and Sanofi and is Founder of IDBiologics, Inc. Vanderbilt University has applied for patents concerning SARS-CoV-2 antibodies that are related to this work. F.E.-H.L., D.C.N., and I.S. are inventors on a patent submitted for the plasmablast survival medium. J.D. and K.W.M. are employees of Berkeley Lights, Inc. All other authors declared no competing interests.

Footnotes

  • Contact information: James E. Crowe, Jr., M.D. [LEAD CONTACT], Departments of Pediatrics, Pathology, Microbiology, and Immunology, and the Vanderbilt Vaccine Center, Mail: Vanderbilt Vaccine Center, 11475 Medical Research Building IV, 2213 Garland Avenue, Nashville, TN 37232-0417, USA, Telephone (615) 343-8064, Email james.crowe{at}vumc.org

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Rapid isolation and profiling of a diverse panel of human monoclonal antibodies targeting the SARS-CoV-2 spike protein
Seth J. Zost, Pavlo Gilchuk, Rita E. Chen, James Brett Case, Joseph X. Reidy, Andrew Trivette, Rachel S. Nargi, Rachel E. Sutton, Naveenchandra Suryadevara, Elaine C. Chen, Elad Binshtein, Swathi Shrihari, Mario Ostrowski, Helen Y. Chu, Jonathan E. Didier, Keith W. MacRenaris, Taylor Jones, Samuel Day, Luke Myers, F. Eun-Hyung Lee, Doan C. Nguyen, Ignacio Sanz, David R. Martinez, Ralph S. Baric, Larissa B. Thackray, Michael S. Diamond, Robert H. Carnahan, James E. Crowe Jr.
bioRxiv 2020.05.12.091462; doi: https://doi.org/10.1101/2020.05.12.091462
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Rapid isolation and profiling of a diverse panel of human monoclonal antibodies targeting the SARS-CoV-2 spike protein
Seth J. Zost, Pavlo Gilchuk, Rita E. Chen, James Brett Case, Joseph X. Reidy, Andrew Trivette, Rachel S. Nargi, Rachel E. Sutton, Naveenchandra Suryadevara, Elaine C. Chen, Elad Binshtein, Swathi Shrihari, Mario Ostrowski, Helen Y. Chu, Jonathan E. Didier, Keith W. MacRenaris, Taylor Jones, Samuel Day, Luke Myers, F. Eun-Hyung Lee, Doan C. Nguyen, Ignacio Sanz, David R. Martinez, Ralph S. Baric, Larissa B. Thackray, Michael S. Diamond, Robert H. Carnahan, James E. Crowe Jr.
bioRxiv 2020.05.12.091462; doi: https://doi.org/10.1101/2020.05.12.091462

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