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Rapid isolation of potent SARS-CoV-2 neutralizing antibodies and protection in a small animal model

Thomas F. Rogers, Fangzhu Zhao, Deli Huang, Nathan Beutler, Alison Burns, Wan-ting He, Oliver Limbo, Chloe Smith, Ge Song, Jordan Woehl, Linlin Yang, Robert K. Abbott, Sean Callaghan, Elijah Garcia, Jonathan Hurtado, Mara Parren, Linghang Peng, James Ricketts, Michael J. Ricciardi, Stephen A. Rawlings, Davey M. Smith, David Nemazee, John R. Teijaro, James E. Voss, Raiees Andrabi, Bryan Briney, Elise Landais, Devin Sok, Joseph G. Jardine, Dennis R. Burton
doi: https://doi.org/10.1101/2020.05.11.088674
Thomas F. Rogers
1Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA
2Division of Infectious Diseases, Department of Medicine, University of California, San Diego, La Jolla, CA 92037, USA
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Fangzhu Zhao
1Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA
3IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA
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Deli Huang
1Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA
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Nathan Beutler
1Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA
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Alison Burns
1Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA
3IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA
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Wan-ting He
1Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA
3IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA
7Consortium for HIV/AIDS Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA
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Oliver Limbo
3IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA
4IAVI, New York, NY10004, USA
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Chloe Smith
1Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA
3IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA
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Ge Song
1Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA
3IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA
7Consortium for HIV/AIDS Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA
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Jordan Woehl
3IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA
4IAVI, New York, NY10004, USA
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Linlin Yang
1Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA
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Robert K. Abbott
5La Jolla Institute for Immunology, La Jolla, CA 92037, USA
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Sean Callaghan
1Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA
3IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA
7Consortium for HIV/AIDS Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA
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Elijah Garcia
1Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA
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Jonathan Hurtado
1Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA
7Consortium for HIV/AIDS Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA
8Center for Viral Systems Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
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Mara Parren
1Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA
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Linghang Peng
1Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA
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James Ricketts
1Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA
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Michael J. Ricciardi
6George Washington University, Washington, DC 20052, USA
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Stephen A. Rawlings
2Division of Infectious Diseases, Department of Medicine, University of California, San Diego, La Jolla, CA 92037, USA
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Davey M. Smith
2Division of Infectious Diseases, Department of Medicine, University of California, San Diego, La Jolla, CA 92037, USA
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David Nemazee
1Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA
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John R. Teijaro
1Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA
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James E. Voss
1Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA
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Raiees Andrabi
1Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA
3IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA
7Consortium for HIV/AIDS Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA
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Bryan Briney
1Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA
7Consortium for HIV/AIDS Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA
8Center for Viral Systems Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
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Elise Landais
3IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA
4IAVI, New York, NY10004, USA
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Devin Sok
1Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA
3IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA
4IAVI, New York, NY10004, USA
7Consortium for HIV/AIDS Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA
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  • For correspondence: burton@scripps.edu
Joseph G. Jardine
3IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA
4IAVI, New York, NY10004, USA
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  • For correspondence: burton@scripps.edu
Dennis R. Burton
1Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA
3IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA
7Consortium for HIV/AIDS Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA
9Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, Cambridge, MA 02139, USA
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  • For correspondence: burton@scripps.edu
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ABSTRACT

The development of countermeasures to prevent and treat COVID-19 is a global health priority. In under 7 weeks, we enrolled a cohort of SARS-CoV-2-recovered participants, developed neutralization assays to interrogate serum and monoclonal antibody responses, adapted our high throughput antibody isolation, production and characterization pipeline to rapidly screen over 1000 antigen-specific antibodies, and established an animal model to test protection. We report multiple highly potent neutralizing antibodies (nAbs) and show that passive transfer of a nAb provides protection against high-dose SARS-CoV-2 challenge in Syrian hamsters. The study suggests a role for nAbs in prophylaxis, and potentially therapy, of COVID-19. The nAbs define protective epitopes to guide vaccine design.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • ↵# Joint first authors

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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. It is made available under a CC-BY 4.0 International license.
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Rapid isolation of potent SARS-CoV-2 neutralizing antibodies and protection in a small animal model
Thomas F. Rogers, Fangzhu Zhao, Deli Huang, Nathan Beutler, Alison Burns, Wan-ting He, Oliver Limbo, Chloe Smith, Ge Song, Jordan Woehl, Linlin Yang, Robert K. Abbott, Sean Callaghan, Elijah Garcia, Jonathan Hurtado, Mara Parren, Linghang Peng, James Ricketts, Michael J. Ricciardi, Stephen A. Rawlings, Davey M. Smith, David Nemazee, John R. Teijaro, James E. Voss, Raiees Andrabi, Bryan Briney, Elise Landais, Devin Sok, Joseph G. Jardine, Dennis R. Burton
bioRxiv 2020.05.11.088674; doi: https://doi.org/10.1101/2020.05.11.088674
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Rapid isolation of potent SARS-CoV-2 neutralizing antibodies and protection in a small animal model
Thomas F. Rogers, Fangzhu Zhao, Deli Huang, Nathan Beutler, Alison Burns, Wan-ting He, Oliver Limbo, Chloe Smith, Ge Song, Jordan Woehl, Linlin Yang, Robert K. Abbott, Sean Callaghan, Elijah Garcia, Jonathan Hurtado, Mara Parren, Linghang Peng, James Ricketts, Michael J. Ricciardi, Stephen A. Rawlings, Davey M. Smith, David Nemazee, John R. Teijaro, James E. Voss, Raiees Andrabi, Bryan Briney, Elise Landais, Devin Sok, Joseph G. Jardine, Dennis R. Burton
bioRxiv 2020.05.11.088674; doi: https://doi.org/10.1101/2020.05.11.088674

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