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Convergent Antibody Responses to SARS-CoV-2 Infection in Convalescent Individuals

Davide F. Robbiani, Christian Gaebler, Frauke Muecksch, Julio C. C. Lorenzi, Zijun Wang, Alice Cho, Marianna Agudelo, Christopher O. Barnes, Anna Gazumyan, Shlomo Finkin, Thomas Hagglof, Thiago Y. Oliveira, Charlotte Viant, Arlene Hurley, Hans-Heinrich Hoffmann, Katrina G. Millard, Rhonda G. Kost, Melissa Cipolla, Kristie Gordon, Filippo Bianchini, Spencer T. Chen, Victor Ramos, Roshni Patel, Juan Dizon, Irina Shimeliovich, Pilar Mendoza, Harald Hartweger, Lilian Nogueira, Maggi Pack, Jill Horowitz, Fabian Schmidt, Yiska Weisblum, Eleftherios Michailidis, Alison W. Ashbrook, Eric Waltari, John E. Pak, Kathryn E. Huey-Tubman, Nicholas Koranda, Pauline R. Hoffman, Anthony P. West Jr., Charles M. Rice, Theodora Hatziioannou, Pamela J. Bjorkman, Paul D. Bieniasz, Marina Caskey, Michel C. Nussenzweig
doi: https://doi.org/10.1101/2020.05.13.092619
Davide F. Robbiani
1Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA
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  • For correspondence: pbieniasz@rockefeller.edu mcaskey@rockefeller.edu nussen@rockefeller.edu drobbiani@rockefeller.edu
Christian Gaebler
1Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA
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Frauke Muecksch
2Laboratory of Retrovirology, The Rockefeller University, New York, NY 10065, USA
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Julio C. C. Lorenzi
1Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA
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Zijun Wang
1Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA
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Alice Cho
1Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA
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Marianna Agudelo
1Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA
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Christopher O. Barnes
6Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA
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Anna Gazumyan
1Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA
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Shlomo Finkin
1Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA
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Thomas Hagglof
1Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA
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Thiago Y. Oliveira
1Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA
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Charlotte Viant
1Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA
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Arlene Hurley
4Hospital Program Direction, The Rockefeller University, New York, NY 10065, USA
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Hans-Heinrich Hoffmann
3Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065, USA
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Katrina G. Millard
1Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA
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Rhonda G. Kost
5Hospital Clinical Research Office, The Rockefeller University, New York, NY 10065, USA
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Melissa Cipolla
1Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA
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Kristie Gordon
1Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA
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Filippo Bianchini
1Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA
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Spencer T. Chen
1Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA
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Victor Ramos
1Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA
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Roshni Patel
1Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA
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Juan Dizon
1Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA
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Irina Shimeliovich
1Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA
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Pilar Mendoza
1Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA
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Harald Hartweger
1Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA
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Lilian Nogueira
1Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA
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Maggi Pack
1Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA
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Jill Horowitz
1Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA
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Fabian Schmidt
2Laboratory of Retrovirology, The Rockefeller University, New York, NY 10065, USA
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Yiska Weisblum
2Laboratory of Retrovirology, The Rockefeller University, New York, NY 10065, USA
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Eleftherios Michailidis
3Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065, USA
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Alison W. Ashbrook
3Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065, USA
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Eric Waltari
7Chan Zuckerberg Biohub, 499 Illinois Street, San Francisco, CA 94158, USA
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John E. Pak
7Chan Zuckerberg Biohub, 499 Illinois Street, San Francisco, CA 94158, USA
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Kathryn E. Huey-Tubman
6Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA
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Nicholas Koranda
6Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA
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Pauline R. Hoffman
6Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA
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Anthony P. West Jr.
6Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA
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Charles M. Rice
3Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065, USA
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Theodora Hatziioannou
2Laboratory of Retrovirology, The Rockefeller University, New York, NY 10065, USA
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Pamela J. Bjorkman
6Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA
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Paul D. Bieniasz
2Laboratory of Retrovirology, The Rockefeller University, New York, NY 10065, USA
8Howard Hughes Medical Institute
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  • For correspondence: pbieniasz@rockefeller.edu mcaskey@rockefeller.edu nussen@rockefeller.edu drobbiani@rockefeller.edu
Marina Caskey
1Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA
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  • For correspondence: pbieniasz@rockefeller.edu mcaskey@rockefeller.edu nussen@rockefeller.edu drobbiani@rockefeller.edu
Michel C. Nussenzweig
1Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA
8Howard Hughes Medical Institute
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  • For correspondence: pbieniasz@rockefeller.edu mcaskey@rockefeller.edu nussen@rockefeller.edu drobbiani@rockefeller.edu
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Abstract

During the COVID-19 pandemic, SARS-CoV-2 infected millions of people and claimed hundreds of thousands of lives. Virus entry into cells depends on the receptor binding domain (RBD) of the SARS-CoV-2 spike protein (S). Although there is no vaccine, it is likely that antibodies will be essential for protection. However, little is known about the human antibody response to SARS-CoV-21–5. Here we report on 149 COVID-19 convalescent individuals. Plasmas collected an average of 39 days after the onset of symptoms had variable half-maximal neutralizing titers ranging from undetectable in 33% to below 1:1000 in 79%, while only 1% showed titers >1:5000. Antibody cloning revealed expanded clones of RBD-specific memory B cells expressing closely related antibodies in different individuals. Despite low plasma titers, antibodies to three distinct epitopes on RBD neutralized at half-maximal inhibitory concentrations (IC50s) as low as single digit ng/mL. Thus, most convalescent plasmas obtained from individuals who recover from COVID-19 do not contain high levels of neutralizing activity. Nevertheless, rare but recurring RBD-specific antibodies with potent antiviral activity were found in all individuals tested, suggesting that a vaccine designed to elicit such antibodies could be broadly effective.

Competing Interest Statement

In connection with this work The Rockefeller University has filed a provisional patent application on which D.F.R. and M.C.N are inventors.

Footnotes

  • This version of the manuscript has been revised to include (i) analysis of 81 additional individuals, including hospitalized; (ii) characterization of 50 additional monoclonal antibodies; (iii) information on cross-reactivity to other coronaviruses; (iv) scripts for bioinformatic analysis of antibodies sequences; (v) structural information for 3 monoclonal antibodies; and (vi) neutralization data with real virus.

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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Convergent Antibody Responses to SARS-CoV-2 Infection in Convalescent Individuals
Davide F. Robbiani, Christian Gaebler, Frauke Muecksch, Julio C. C. Lorenzi, Zijun Wang, Alice Cho, Marianna Agudelo, Christopher O. Barnes, Anna Gazumyan, Shlomo Finkin, Thomas Hagglof, Thiago Y. Oliveira, Charlotte Viant, Arlene Hurley, Hans-Heinrich Hoffmann, Katrina G. Millard, Rhonda G. Kost, Melissa Cipolla, Kristie Gordon, Filippo Bianchini, Spencer T. Chen, Victor Ramos, Roshni Patel, Juan Dizon, Irina Shimeliovich, Pilar Mendoza, Harald Hartweger, Lilian Nogueira, Maggi Pack, Jill Horowitz, Fabian Schmidt, Yiska Weisblum, Eleftherios Michailidis, Alison W. Ashbrook, Eric Waltari, John E. Pak, Kathryn E. Huey-Tubman, Nicholas Koranda, Pauline R. Hoffman, Anthony P. West Jr., Charles M. Rice, Theodora Hatziioannou, Pamela J. Bjorkman, Paul D. Bieniasz, Marina Caskey, Michel C. Nussenzweig
bioRxiv 2020.05.13.092619; doi: https://doi.org/10.1101/2020.05.13.092619
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Convergent Antibody Responses to SARS-CoV-2 Infection in Convalescent Individuals
Davide F. Robbiani, Christian Gaebler, Frauke Muecksch, Julio C. C. Lorenzi, Zijun Wang, Alice Cho, Marianna Agudelo, Christopher O. Barnes, Anna Gazumyan, Shlomo Finkin, Thomas Hagglof, Thiago Y. Oliveira, Charlotte Viant, Arlene Hurley, Hans-Heinrich Hoffmann, Katrina G. Millard, Rhonda G. Kost, Melissa Cipolla, Kristie Gordon, Filippo Bianchini, Spencer T. Chen, Victor Ramos, Roshni Patel, Juan Dizon, Irina Shimeliovich, Pilar Mendoza, Harald Hartweger, Lilian Nogueira, Maggi Pack, Jill Horowitz, Fabian Schmidt, Yiska Weisblum, Eleftherios Michailidis, Alison W. Ashbrook, Eric Waltari, John E. Pak, Kathryn E. Huey-Tubman, Nicholas Koranda, Pauline R. Hoffman, Anthony P. West Jr., Charles M. Rice, Theodora Hatziioannou, Pamela J. Bjorkman, Paul D. Bieniasz, Marina Caskey, Michel C. Nussenzweig
bioRxiv 2020.05.13.092619; doi: https://doi.org/10.1101/2020.05.13.092619

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