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LY-CoV555, a rapidly isolated potent neutralizing antibody, provides protection in a non-human primate model of SARS-CoV-2 infection

View ORCID ProfileBryan E. Jones, Patricia L. Brown-Augsburger, Kizzmekia S. Corbett, Kathryn Westendorf, Julian Davies, Thomas P. Cujec, Christopher M. Wiethoff, Jamie L. Blackbourne, Beverly A. Heinz, Denisa Foster, Richard E. Higgs, Deepa Balasubramaniam, Lingshu Wang, Roza Bidshahri, Lucas Kraft, Yuri Hwang, Stefanie Žentelis, Kevin R. Jepson, Rodrigo Goya, Maia A. Smith, David W. Collins, Samuel J. Hinshaw, Sean A. Tycho, Davide Pellacani, Ping Xiang, Krithika Muthuraman, Solmaz Sobhanifar, Marissa H. Piper, Franz J. Triana, Jorg Hendle, Anna Pustilnik, Andrew C. Adams, Shawn J. Berens, Ralph S. Baric, David R. Martinez, Robert W. Cross, Thomas W. Geisbert, Viktoriya Borisevich, Olubukola Abiona, Hayley M. Belli, Maren de Vries, Adil Mohamed, Meike Dittmann, Marie Samanovic, Mark J. Mulligan, Jory A. Goldsmith, Ching-Lin Hsieh, Nicole V. Johnson, Daniel Wrapp, Jason S. McLellan, Bryan C. Barnhart, Barney S. Graham, John R. Mascola, Carl L. Hansen, View ORCID ProfileEster Falconer
doi: https://doi.org/10.1101/2020.09.30.318972
Bryan E. Jones
1Lilly Biotechnology Center, Eli Lilly and Company, San Diego, CA, USA
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  • ORCID record for Bryan E. Jones
  • For correspondence: jones_bryan_edward@lilly.com ester.falconer@abcellera.com
Patricia L. Brown-Augsburger
2Eli Lilly and Company, Indianapolis, IN, USA
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Kizzmekia S. Corbett
3Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
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Kathryn Westendorf
4AbCellera Biologics Inc., Vancouver, BC, Canada
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Julian Davies
1Lilly Biotechnology Center, Eli Lilly and Company, San Diego, CA, USA
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Thomas P. Cujec
1Lilly Biotechnology Center, Eli Lilly and Company, San Diego, CA, USA
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Christopher M. Wiethoff
2Eli Lilly and Company, Indianapolis, IN, USA
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Jamie L. Blackbourne
2Eli Lilly and Company, Indianapolis, IN, USA
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Beverly A. Heinz
2Eli Lilly and Company, Indianapolis, IN, USA
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Denisa Foster
1Lilly Biotechnology Center, Eli Lilly and Company, San Diego, CA, USA
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Richard E. Higgs
2Eli Lilly and Company, Indianapolis, IN, USA
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Deepa Balasubramaniam
1Lilly Biotechnology Center, Eli Lilly and Company, San Diego, CA, USA
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Lingshu Wang
3Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
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Roza Bidshahri
4AbCellera Biologics Inc., Vancouver, BC, Canada
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Lucas Kraft
4AbCellera Biologics Inc., Vancouver, BC, Canada
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Yuri Hwang
4AbCellera Biologics Inc., Vancouver, BC, Canada
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Stefanie Žentelis
4AbCellera Biologics Inc., Vancouver, BC, Canada
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Kevin R. Jepson
4AbCellera Biologics Inc., Vancouver, BC, Canada
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Rodrigo Goya
4AbCellera Biologics Inc., Vancouver, BC, Canada
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Maia A. Smith
4AbCellera Biologics Inc., Vancouver, BC, Canada
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David W. Collins
4AbCellera Biologics Inc., Vancouver, BC, Canada
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Samuel J. Hinshaw
4AbCellera Biologics Inc., Vancouver, BC, Canada
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Sean A. Tycho
4AbCellera Biologics Inc., Vancouver, BC, Canada
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Davide Pellacani
4AbCellera Biologics Inc., Vancouver, BC, Canada
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Ping Xiang
4AbCellera Biologics Inc., Vancouver, BC, Canada
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Krithika Muthuraman
4AbCellera Biologics Inc., Vancouver, BC, Canada
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Solmaz Sobhanifar
4AbCellera Biologics Inc., Vancouver, BC, Canada
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Marissa H. Piper
1Lilly Biotechnology Center, Eli Lilly and Company, San Diego, CA, USA
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Franz J. Triana
1Lilly Biotechnology Center, Eli Lilly and Company, San Diego, CA, USA
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Jorg Hendle
1Lilly Biotechnology Center, Eli Lilly and Company, San Diego, CA, USA
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Anna Pustilnik
1Lilly Biotechnology Center, Eli Lilly and Company, San Diego, CA, USA
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Andrew C. Adams
2Eli Lilly and Company, Indianapolis, IN, USA
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Shawn J. Berens
2Eli Lilly and Company, Indianapolis, IN, USA
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Ralph S. Baric
5University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
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David R. Martinez
5University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
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Robert W. Cross
6Galveston National Laboratory, University of Texas Medical Branch, Galveston, TX; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA
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Thomas W. Geisbert
6Galveston National Laboratory, University of Texas Medical Branch, Galveston, TX; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA
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Viktoriya Borisevich
6Galveston National Laboratory, University of Texas Medical Branch, Galveston, TX; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA
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Olubukola Abiona
3Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
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Hayley M. Belli
7Department of Population Health, Division of Biostatistics, New York University Grossman School of Medicine, New York, NY, USA
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Maren de Vries
8Department of Microbiology, New York University Grossman School of Medicine, New York, NY, USA
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Adil Mohamed
8Department of Microbiology, New York University Grossman School of Medicine, New York, NY, USA
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Meike Dittmann
8Department of Microbiology, New York University Grossman School of Medicine, New York, NY, USA
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Marie Samanovic
9NYU Langone Vaccine Center, Department of Medicine, Division of Infectious Diseases and Immunology, New York University Grossman School of Medicine, New York, NY, USA
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Mark J. Mulligan
9NYU Langone Vaccine Center, Department of Medicine, Division of Infectious Diseases and Immunology, New York University Grossman School of Medicine, New York, NY, USA
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Jory A. Goldsmith
10Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA
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Ching-Lin Hsieh
10Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA
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Nicole V. Johnson
10Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA
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Daniel Wrapp
10Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA
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Jason S. McLellan
10Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA
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Bryan C. Barnhart
4AbCellera Biologics Inc., Vancouver, BC, Canada
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Barney S. Graham
3Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
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John R. Mascola
3Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
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Carl L. Hansen
4AbCellera Biologics Inc., Vancouver, BC, Canada
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Ester Falconer
4AbCellera Biologics Inc., Vancouver, BC, Canada
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  • ORCID record for Ester Falconer
  • For correspondence: jones_bryan_edward@lilly.com ester.falconer@abcellera.com
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Abstract

SARS-CoV-2 poses a public health threat for which therapeutic agents are urgently needed. Herein, we report that high-throughput microfluidic screening of antigen-specific B-cells led to the identification of LY-CoV555, a potent anti-spike neutralizing antibody from a convalescent COVID-19 patient. Biochemical, structural, and functional characterization revealed high-affinity binding to the receptor-binding domain, ACE2 binding inhibition, and potent neutralizing activity. In a rhesus macaque challenge model, prophylaxis doses as low as 2.5 mg/kg reduced viral replication in the upper and lower respiratory tract. These data demonstrate that high-throughput screening can lead to the identification of a potent antiviral antibody that protects against SARS-CoV-2 infection.

One Sentence Summary LY-CoV555, an anti-spike antibody derived from a convalescent COVID-19 patient, potently neutralizes SARS-CoV-2 and protects the upper and lower airways of non-human primates against SARS-CoV-2 infection.

Competing Interest Statement

M.J.M. has research grant funding from NIH/NIAID, Pfizer, and Sanofi; and personal fees from Meissa Vaccines, Inc. B.E.J., P.LB., J.D., T.P.C., C.M.W., J.L.B., B.A.H., R.E.H., D.B., D.F., M.H.P., F.J.T., J.H., A.P., A.C.A. and S.J.B. are employees and stockholders of Eli Lilly and Company. K.W., R.B., L.K., S.J.H., S.S., B.C.B, and E.F. are employees of AbCellera Biologics Inc. C.L.H., R.G., D.P., P.X., Y.H., R.B., K.R.J. M.A.S., S.Z., D.W.C., and S.A.T. are employees and stockholders of AbCellera Biologics Inc.. K.M. is a former employee and stockholder of AbCellera Biologics Inc. M.D. received a contract from Eli Lilly and Company to support the studies reported herein. Authors from AbCellera Biologics Inc., National Institute of Allergy and Infectious Diseases (K.S.C., B.S.G., and J.R.M.), and Eli Lilly and Company are inventors on patent applications related to the work described here. R.S.B., D.R.M., R.W.C., T.W.G, V.B., O.A., L.W., H.M.B., M.D.V., A.D., M.S., J.A.G., C.L.H., N.V.J., J.S.M., and D.W. declare no competing interests.

Footnotes

  • References have been updated in the main text and supplemental

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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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LY-CoV555, a rapidly isolated potent neutralizing antibody, provides protection in a non-human primate model of SARS-CoV-2 infection
Bryan E. Jones, Patricia L. Brown-Augsburger, Kizzmekia S. Corbett, Kathryn Westendorf, Julian Davies, Thomas P. Cujec, Christopher M. Wiethoff, Jamie L. Blackbourne, Beverly A. Heinz, Denisa Foster, Richard E. Higgs, Deepa Balasubramaniam, Lingshu Wang, Roza Bidshahri, Lucas Kraft, Yuri Hwang, Stefanie Žentelis, Kevin R. Jepson, Rodrigo Goya, Maia A. Smith, David W. Collins, Samuel J. Hinshaw, Sean A. Tycho, Davide Pellacani, Ping Xiang, Krithika Muthuraman, Solmaz Sobhanifar, Marissa H. Piper, Franz J. Triana, Jorg Hendle, Anna Pustilnik, Andrew C. Adams, Shawn J. Berens, Ralph S. Baric, David R. Martinez, Robert W. Cross, Thomas W. Geisbert, Viktoriya Borisevich, Olubukola Abiona, Hayley M. Belli, Maren de Vries, Adil Mohamed, Meike Dittmann, Marie Samanovic, Mark J. Mulligan, Jory A. Goldsmith, Ching-Lin Hsieh, Nicole V. Johnson, Daniel Wrapp, Jason S. McLellan, Bryan C. Barnhart, Barney S. Graham, John R. Mascola, Carl L. Hansen, Ester Falconer
bioRxiv 2020.09.30.318972; doi: https://doi.org/10.1101/2020.09.30.318972
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LY-CoV555, a rapidly isolated potent neutralizing antibody, provides protection in a non-human primate model of SARS-CoV-2 infection
Bryan E. Jones, Patricia L. Brown-Augsburger, Kizzmekia S. Corbett, Kathryn Westendorf, Julian Davies, Thomas P. Cujec, Christopher M. Wiethoff, Jamie L. Blackbourne, Beverly A. Heinz, Denisa Foster, Richard E. Higgs, Deepa Balasubramaniam, Lingshu Wang, Roza Bidshahri, Lucas Kraft, Yuri Hwang, Stefanie Žentelis, Kevin R. Jepson, Rodrigo Goya, Maia A. Smith, David W. Collins, Samuel J. Hinshaw, Sean A. Tycho, Davide Pellacani, Ping Xiang, Krithika Muthuraman, Solmaz Sobhanifar, Marissa H. Piper, Franz J. Triana, Jorg Hendle, Anna Pustilnik, Andrew C. Adams, Shawn J. Berens, Ralph S. Baric, David R. Martinez, Robert W. Cross, Thomas W. Geisbert, Viktoriya Borisevich, Olubukola Abiona, Hayley M. Belli, Maren de Vries, Adil Mohamed, Meike Dittmann, Marie Samanovic, Mark J. Mulligan, Jory A. Goldsmith, Ching-Lin Hsieh, Nicole V. Johnson, Daniel Wrapp, Jason S. McLellan, Bryan C. Barnhart, Barney S. Graham, John R. Mascola, Carl L. Hansen, Ester Falconer
bioRxiv 2020.09.30.318972; doi: https://doi.org/10.1101/2020.09.30.318972

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