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Characterization of neutralizing antibodies from a SARS-CoV-2 infected individual

Emilie Seydoux, Leah J. Homad, Anna J. MacCamy, K. Rachael Parks, Nicholas K. Hurlburt, Madeleine F. Jennewein, Nicholas R. Akins, Andrew B. Stuart, Yu-Hsin Wan, Junli Feng, Rachael E. Nelson, Suruchi Singh, Kristen W. Cohen, M. Juliana McElrath, Janet A. Englund, Helen Y. Chu, Marie Pancera, Andrew T. McGuire, Leonidas Stamatatos
doi: https://doi.org/10.1101/2020.05.12.091298
Emilie Seydoux
1Fred Hutchinson Cancer Research Center, Vaccines and Infectious Diseases Division, Seattle, WA, USA
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Leah J. Homad
1Fred Hutchinson Cancer Research Center, Vaccines and Infectious Diseases Division, Seattle, WA, USA
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Anna J. MacCamy
1Fred Hutchinson Cancer Research Center, Vaccines and Infectious Diseases Division, Seattle, WA, USA
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K. Rachael Parks
1Fred Hutchinson Cancer Research Center, Vaccines and Infectious Diseases Division, Seattle, WA, USA
2University of Washington, Department of Global Health, Seattle, WA, USA
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Nicholas K. Hurlburt
1Fred Hutchinson Cancer Research Center, Vaccines and Infectious Diseases Division, Seattle, WA, USA
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Madeleine F. Jennewein
1Fred Hutchinson Cancer Research Center, Vaccines and Infectious Diseases Division, Seattle, WA, USA
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Nicholas R. Akins
1Fred Hutchinson Cancer Research Center, Vaccines and Infectious Diseases Division, Seattle, WA, USA
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Andrew B. Stuart
1Fred Hutchinson Cancer Research Center, Vaccines and Infectious Diseases Division, Seattle, WA, USA
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Yu-Hsin Wan
1Fred Hutchinson Cancer Research Center, Vaccines and Infectious Diseases Division, Seattle, WA, USA
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Junli Feng
1Fred Hutchinson Cancer Research Center, Vaccines and Infectious Diseases Division, Seattle, WA, USA
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Rachael E. Nelson
1Fred Hutchinson Cancer Research Center, Vaccines and Infectious Diseases Division, Seattle, WA, USA
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Suruchi Singh
1Fred Hutchinson Cancer Research Center, Vaccines and Infectious Diseases Division, Seattle, WA, USA
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Kristen W. Cohen
1Fred Hutchinson Cancer Research Center, Vaccines and Infectious Diseases Division, Seattle, WA, USA
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M. Juliana McElrath
1Fred Hutchinson Cancer Research Center, Vaccines and Infectious Diseases Division, Seattle, WA, USA
2University of Washington, Department of Global Health, Seattle, WA, USA
3Department of Medicine, University of Washington, Seattle, WA, USA
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Janet A. Englund
4Department of Pediatrics, University of Washington and Seattle Children’s Research, Seattle, WA, USA
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Helen Y. Chu
3Department of Medicine, University of Washington, Seattle, WA, USA
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Marie Pancera
1Fred Hutchinson Cancer Research Center, Vaccines and Infectious Diseases Division, Seattle, WA, USA
5Vaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institute of Health, Bethesda, MD, USA
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  • For correspondence: lstamata@fredhutch.org amcguire@fredhutch.org mpancera@fredhutch.org
Andrew T. McGuire
1Fred Hutchinson Cancer Research Center, Vaccines and Infectious Diseases Division, Seattle, WA, USA
2University of Washington, Department of Global Health, Seattle, WA, USA
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  • For correspondence: lstamata@fredhutch.org amcguire@fredhutch.org mpancera@fredhutch.org
Leonidas Stamatatos
1Fred Hutchinson Cancer Research Center, Vaccines and Infectious Diseases Division, Seattle, WA, USA
2University of Washington, Department of Global Health, Seattle, WA, USA
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  • For correspondence: lstamata@fredhutch.org amcguire@fredhutch.org mpancera@fredhutch.org
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ABSTRACT

B cells specific for the SARS-CoV-2 S envelope glycoprotein spike were isolated from a COVID-19-infected subject using a stabilized spike-derived ectodomain (S2P) twenty-one days post-infection. Forty-four S2P-specific monoclonal antibodies were generated, three of which bound to the receptor binding domain (RBD). The antibodies were minimally mutated from germline and were derived from different B cell lineages. Only two antibodies displayed neutralizing activity against SARS-CoV-2 pseudo-virus. The most potent antibody bound the RBD in a manner that prevented binding to the ACE2 receptor, while the other bound outside the RBD. Our study indicates that the majority of antibodies against the viral envelope spike that were generated during the first weeks of COVID-19 infection are non-neutralizing and target epitopes outside the RBD. Antibodies that disrupt the SARS-CoV-2 spike-ACE2 interaction can potently neutralize the virus without undergoing extensive maturation. Such antibodies have potential preventive/therapeutic potential and can serve as templates for vaccine-design.

IN BRIEF SARS-CoV-2 infection leads to expansion of diverse B cells clones against the viral spike glycoprotein (S). The antibodies bind S with high affinity despite being minimally mutated. Thus, the development of neutralizing antibody responses by vaccination will require the activation of certain naïve B cells without requiring extensive somatic mutation.

Highlights

  • Analysis of early B cell response to SARS-CoV-2 spike protein

  • Most antibodies target non-neutralizing epitopes

  • Potent neutralizing mAb blocks the interaction of the S protein with ACE2

  • Neutralizing antibodies are minimally mutated

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
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-NC-ND 4.0 International license.
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Posted May 12, 2020.
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Characterization of neutralizing antibodies from a SARS-CoV-2 infected individual
Emilie Seydoux, Leah J. Homad, Anna J. MacCamy, K. Rachael Parks, Nicholas K. Hurlburt, Madeleine F. Jennewein, Nicholas R. Akins, Andrew B. Stuart, Yu-Hsin Wan, Junli Feng, Rachael E. Nelson, Suruchi Singh, Kristen W. Cohen, M. Juliana McElrath, Janet A. Englund, Helen Y. Chu, Marie Pancera, Andrew T. McGuire, Leonidas Stamatatos
bioRxiv 2020.05.12.091298; doi: https://doi.org/10.1101/2020.05.12.091298
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Characterization of neutralizing antibodies from a SARS-CoV-2 infected individual
Emilie Seydoux, Leah J. Homad, Anna J. MacCamy, K. Rachael Parks, Nicholas K. Hurlburt, Madeleine F. Jennewein, Nicholas R. Akins, Andrew B. Stuart, Yu-Hsin Wan, Junli Feng, Rachael E. Nelson, Suruchi Singh, Kristen W. Cohen, M. Juliana McElrath, Janet A. Englund, Helen Y. Chu, Marie Pancera, Andrew T. McGuire, Leonidas Stamatatos
bioRxiv 2020.05.12.091298; doi: https://doi.org/10.1101/2020.05.12.091298

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