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Antibody potency, effector function and combinations in protection from SARS-CoV-2 infection in vivo

Alexandra Schäfer, Frauke Muecksch, Julio C. C. Lorenzi, Sarah R. Leist, Melissa Cipolla, Stylianos Bournazos, Fabian Schmidt, Anna Gazumyan, Ralph S. Baric, Davide F. Robbiani, Theodora Hatziioannou, Jeffrey V. Ravetch, Paul D. Bieniasz, Michel C. Nussenzweig, View ORCID ProfileTimothy P. Sheahan
doi: https://doi.org/10.1101/2020.09.15.298067
Alexandra Schäfer
1Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599
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Frauke Muecksch
2Laboratory of Retrovirology, The Rockefeller University, New York, NY, 10065
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Julio C. C. Lorenzi
3Laboratory of Molecular Immunology, Rockefeller University, New York, NY 10065
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Sarah R. Leist
1Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599
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Melissa Cipolla
3Laboratory of Molecular Immunology, Rockefeller University, New York, NY 10065
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Stylianos Bournazos
4Laboratory of Molecular Genetics and Immunology, The Rockefeller University, New York, NY, 10065
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Fabian Schmidt
2Laboratory of Retrovirology, The Rockefeller University, New York, NY, 10065
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Anna Gazumyan
3Laboratory of Molecular Immunology, Rockefeller University, New York, NY 10065
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Ralph S. Baric
1Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599
5Department of Microbiology & Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
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Davide F. Robbiani
2Laboratory of Retrovirology, The Rockefeller University, New York, NY, 10065
6Institute for Research in Biomedicine, Università della Svizzera italiana, Bellinzona, Switzerland
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Theodora Hatziioannou
2Laboratory of Retrovirology, The Rockefeller University, New York, NY, 10065
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Jeffrey V. Ravetch
4Laboratory of Molecular Genetics and Immunology, The Rockefeller University, New York, NY, 10065
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Paul D. Bieniasz
2Laboratory of Retrovirology, The Rockefeller University, New York, NY, 10065
7Howard Hughes Medical Institute, The Rockefeller University, New York, NY, 10065
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Michel C. Nussenzweig
3Laboratory of Molecular Immunology, Rockefeller University, New York, NY 10065
7Howard Hughes Medical Institute, The Rockefeller University, New York, NY, 10065
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  • For correspondence: nussen@rockefeller.edu sheahan@email.unc.edu
Timothy P. Sheahan
1Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599
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  • ORCID record for Timothy P. Sheahan
  • For correspondence: nussen@rockefeller.edu sheahan@email.unc.edu
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Abstract

SARS-CoV-2, the causative agent of COVID-19, is responsible for over 24 million infections and 800,000 deaths since its emergence in December 2019. There are few therapeutic options and no approved vaccines. Here we examine the properties of highly potent human monoclonal antibodies (hu-mAbs) in a mouse adapted model of SARS-CoV-2 infection (SARS-CoV-2 MA). In vitro antibody neutralization potency did not uniformly correlate with in vivo activity, and some hu-mAbs were more potent in combination in vivo. Analysis of antibody Fc regions revealed that binding to activating Fc receptors is essential for optimal protection against SARS-CoV-2 MA. The data indicate that hu-mAb protective activity is dependent on intact effector function and that in vivo testing is required to establish optimal hu-mAb combinations for COVID-19 prevention.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • Summary Human monoclonal antibody potency in vitro does not uniformly correlate with their in vivo neutralization of SARS-CoV-2. Antibody Fc effector function is important for in vivo neutralization and antibody combinations show superior efficacy compared to single antibodies.

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-ND 4.0 International license.
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Posted September 15, 2020.
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Antibody potency, effector function and combinations in protection from SARS-CoV-2 infection in vivo
Alexandra Schäfer, Frauke Muecksch, Julio C. C. Lorenzi, Sarah R. Leist, Melissa Cipolla, Stylianos Bournazos, Fabian Schmidt, Anna Gazumyan, Ralph S. Baric, Davide F. Robbiani, Theodora Hatziioannou, Jeffrey V. Ravetch, Paul D. Bieniasz, Michel C. Nussenzweig, Timothy P. Sheahan
bioRxiv 2020.09.15.298067; doi: https://doi.org/10.1101/2020.09.15.298067
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Antibody potency, effector function and combinations in protection from SARS-CoV-2 infection in vivo
Alexandra Schäfer, Frauke Muecksch, Julio C. C. Lorenzi, Sarah R. Leist, Melissa Cipolla, Stylianos Bournazos, Fabian Schmidt, Anna Gazumyan, Ralph S. Baric, Davide F. Robbiani, Theodora Hatziioannou, Jeffrey V. Ravetch, Paul D. Bieniasz, Michel C. Nussenzweig, Timothy P. Sheahan
bioRxiv 2020.09.15.298067; doi: https://doi.org/10.1101/2020.09.15.298067

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