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Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants

Yiska Weisblum, Fabian Schmidt, Fengwen Zhang, Justin DaSilva, Daniel Poston, Julio C. C. Lorenzi, Frauke Muecksch, Magdalena Rutkowska, Hans-Heinrich Hoffmann, Eleftherios Michailidis, Christian Gaebler, Marianna Agudelo, Alice Cho, Zijun Wang, Anna Gazumyan, Melissa Cipolla, Larry Luchsinger, Christopher D. Hillyer, Marina Caskey, Davide F. Robbiani, Charles M. Rice, Michel C. Nussenzweig, Theodora Hatziioannou, View ORCID ProfilePaul D. Bieniasz
doi: https://doi.org/10.1101/2020.07.21.214759
Yiska Weisblum
1Laboratory of Retrovirology, The Rockefeller University, 1230 York Avenue, New York NY 10065
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Fabian Schmidt
1Laboratory of Retrovirology, The Rockefeller University, 1230 York Avenue, New York NY 10065
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Fengwen Zhang
1Laboratory of Retrovirology, The Rockefeller University, 1230 York Avenue, New York NY 10065
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Justin DaSilva
1Laboratory of Retrovirology, The Rockefeller University, 1230 York Avenue, New York NY 10065
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Daniel Poston
1Laboratory of Retrovirology, The Rockefeller University, 1230 York Avenue, New York NY 10065
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Julio C. C. Lorenzi
2Laboratory of Molecular Immunology The Rockefeller University, 1230 York Avenue, New York NY 10065
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Frauke Muecksch
1Laboratory of Retrovirology, The Rockefeller University, 1230 York Avenue, New York NY 10065
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Magdalena Rutkowska
1Laboratory of Retrovirology, The Rockefeller University, 1230 York Avenue, New York NY 10065
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Hans-Heinrich Hoffmann
3Laboratory of Virology and Infectious Disease The Rockefeller University, 1230 York Avenue, New York NY 10065
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Eleftherios Michailidis
3Laboratory of Virology and Infectious Disease The Rockefeller University, 1230 York Avenue, New York NY 10065
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Christian Gaebler
2Laboratory of Molecular Immunology The Rockefeller University, 1230 York Avenue, New York NY 10065
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Marianna Agudelo
2Laboratory of Molecular Immunology The Rockefeller University, 1230 York Avenue, New York NY 10065
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Alice Cho
2Laboratory of Molecular Immunology The Rockefeller University, 1230 York Avenue, New York NY 10065
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Zijun Wang
2Laboratory of Molecular Immunology The Rockefeller University, 1230 York Avenue, New York NY 10065
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Anna Gazumyan
2Laboratory of Molecular Immunology The Rockefeller University, 1230 York Avenue, New York NY 10065
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Melissa Cipolla
2Laboratory of Molecular Immunology The Rockefeller University, 1230 York Avenue, New York NY 10065
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Larry Luchsinger
4Lindsley F. Kimball Research Institute, New York Blood Center,New York, NY 10065
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Christopher D. Hillyer
4Lindsley F. Kimball Research Institute, New York Blood Center,New York, NY 10065
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Marina Caskey
2Laboratory of Molecular Immunology The Rockefeller University, 1230 York Avenue, New York NY 10065
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Davide F. Robbiani
2Laboratory of Molecular Immunology The Rockefeller University, 1230 York Avenue, New York NY 10065
5Institute for Research in Biomedicine, Università della Svizzera italiana, Bellinzona, Switzerland
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Charles M. Rice
3Laboratory of Virology and Infectious Disease The Rockefeller University, 1230 York Avenue, New York NY 10065
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Michel C. Nussenzweig
2Laboratory of Molecular Immunology The Rockefeller University, 1230 York Avenue, New York NY 10065
6Howard Hughes Medical Institute, The Rockefeller University, 1230 York Avenue, New York NY 10065
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  • For correspondence: thatziio@rockefeller.edu pbieniasz@rockefeller.edu
Theodora Hatziioannou
1Laboratory of Retrovirology, The Rockefeller University, 1230 York Avenue, New York NY 10065
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Paul D. Bieniasz
1Laboratory of Retrovirology, The Rockefeller University, 1230 York Avenue, New York NY 10065
6Howard Hughes Medical Institute, The Rockefeller University, 1230 York Avenue, New York NY 10065
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  • ORCID record for Paul D. Bieniasz
  • For correspondence: thatziio@rockefeller.edu pbieniasz@rockefeller.edu
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Abstract

Neutralizing antibodies elicited by prior infection or vaccination are likely to be key for future protection of individuals and populations against SARS-CoV-2. Moreover, passively administered antibodies are among the most promising therapeutic and prophylactic anti-SARS-CoV-2 agents. However, the degree to which SARS-CoV-2 will adapt to evade neutralizing antibodies is unclear. Using a recombinant chimeric VSV/SARS-CoV-2 reporter virus, we show that functional SARS-CoV-2 S protein variants with mutations in the receptor binding domain (RBD) and N-terminal domain that confer resistance to monoclonal antibodies or convalescent plasma can be readily selected. Notably, SARS-CoV-2 S variants that resist commonly elicited neutralizing antibodies are now present at low frequencies in circulating SARS-CoV-2 populations. Finally, the emergence of antibody-resistant SARS-CoV-2 variants that might limit the therapeutic usefulness of monoclonal antibodies can be mitigated by the use of antibody combinations that target distinct neutralizing epitopes.

Competing Interest Statement

Patent applications submitted by Rockefeller University are pending for anti SARS-CoV-2 antibodies (MCN, DR, inventors) and VSV/SARS-CoV-2 chimeric virus (PDB, TH, FS and YW, inventors)

Copyright 
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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Posted July 22, 2020.
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Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants
Yiska Weisblum, Fabian Schmidt, Fengwen Zhang, Justin DaSilva, Daniel Poston, Julio C. C. Lorenzi, Frauke Muecksch, Magdalena Rutkowska, Hans-Heinrich Hoffmann, Eleftherios Michailidis, Christian Gaebler, Marianna Agudelo, Alice Cho, Zijun Wang, Anna Gazumyan, Melissa Cipolla, Larry Luchsinger, Christopher D. Hillyer, Marina Caskey, Davide F. Robbiani, Charles M. Rice, Michel C. Nussenzweig, Theodora Hatziioannou, Paul D. Bieniasz
bioRxiv 2020.07.21.214759; doi: https://doi.org/10.1101/2020.07.21.214759
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Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants
Yiska Weisblum, Fabian Schmidt, Fengwen Zhang, Justin DaSilva, Daniel Poston, Julio C. C. Lorenzi, Frauke Muecksch, Magdalena Rutkowska, Hans-Heinrich Hoffmann, Eleftherios Michailidis, Christian Gaebler, Marianna Agudelo, Alice Cho, Zijun Wang, Anna Gazumyan, Melissa Cipolla, Larry Luchsinger, Christopher D. Hillyer, Marina Caskey, Davide F. Robbiani, Charles M. Rice, Michel C. Nussenzweig, Theodora Hatziioannou, Paul D. Bieniasz
bioRxiv 2020.07.21.214759; doi: https://doi.org/10.1101/2020.07.21.214759

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