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Evolution of Antibody Immunity to SARS-CoV-2

Christian Gaebler, Zijun Wang, Julio C. C. Lorenzi, Frauke Muecksch, Shlomo Finkin, Minami Tokuyama, Alice Cho, Mila Jankovic, Dennis Schaefer-Babajew, Thiago Y. Oliveira, Melissa Cipolla, Charlotte Viant, Christopher O. Barnes, Yaron Bram, Gaëlle Breton, Thomas Hägglöf, Pilar Mendoza, Arlene Hurley, Martina Turroja, Kristie Gordon, Katrina G. Millard, Victor Ramos, Fabian Schmidt, Yiska Weisblum, Divya Jha, Michael Tankelevich, Gustavo Martinez-Delgado, Jim Yee, Roshni Patel, Juan Dizon, Cecille Unson-O’Brien, Irina Shimeliovich, Davide F. Robbiani, Zhen Zhao, Anna Gazumyan, Robert E. Schwartz, Theodora Hatziioannou, Pamela J. Bjorkman, Saurabh Mehandru, Paul D. Bieniasz, Marina Caskey, Michel C. Nussenzweig
doi: https://doi.org/10.1101/2020.11.03.367391
Christian Gaebler
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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Julio C. C. Lorenzi
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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Shlomo Finkin
1Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA
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Minami Tokuyama
3Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
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Alice Cho
1Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA
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Mila Jankovic
1Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA
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Dennis Schaefer-Babajew
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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Melissa Cipolla
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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Christopher O. Barnes
4Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA
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Yaron Bram
5Division of Gastroenterology and Hepatology, Department of Medicine, Weill Cornell Medicine, New York, NY 10065, USA
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Gaëlle Breton
1Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA
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Thomas Hägglöf
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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Arlene Hurley
6Hospital Program Direction, The Rockefeller University, New York, NY 10065, USA
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Martina Turroja
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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Katrina G. Millard
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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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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Divya Jha
3Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
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Michael Tankelevich
3Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
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Gustavo Martinez-Delgado
3Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
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Jim Yee
7Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, 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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Cecille Unson-O’Brien
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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Davide F. Robbiani
8Institute for Research in Biomedicine, Università della Svizzera italiana, Bellinzona, Switzerland
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Zhen Zhao
7Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY 10065, USA
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Anna Gazumyan
1Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA
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Robert E. Schwartz
5Division of Gastroenterology and Hepatology, Department of Medicine, Weill Cornell Medicine, New York, NY 10065, USA
9Department of Physiology, Biophysics and Systems Biology, Weill Cornell Medicine, 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
4Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA
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Saurabh Mehandru
3Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
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  • For correspondence: saurabh.mehandru@mssm.edu pbieniasz@rockefeller.edu mcaskey@rockefeller.edu nussen@rockefeller.edu
Paul D. Bieniasz
2Laboratory of Retrovirology, The Rockefeller University, New York, NY 10065, USA
10Howard Hughes Medical Institute
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  • For correspondence: saurabh.mehandru@mssm.edu pbieniasz@rockefeller.edu mcaskey@rockefeller.edu nussen@rockefeller.edu
Marina Caskey
1Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA
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  • For correspondence: saurabh.mehandru@mssm.edu pbieniasz@rockefeller.edu mcaskey@rockefeller.edu nussen@rockefeller.edu
Michel C. Nussenzweig
1Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA
10Howard Hughes Medical Institute
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  • For correspondence: saurabh.mehandru@mssm.edu pbieniasz@rockefeller.edu mcaskey@rockefeller.edu nussen@rockefeller.edu
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Abstract

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has infected 78 million individuals and is responsible for over 1.7 million deaths to date. Infection is associated with development of variable levels of antibodies with neutralizing activity that can protect against infection in animal models. Antibody levels decrease with time, but the nature and quality of the memory B cells that would be called upon to produce antibodies upon re-infection has not been examined. Here we report on the humoral memory response in a cohort of 87 individuals assessed at 1.3 and 6.2 months after infection. We find that IgM, and IgG anti-SARS-CoV-2 spike protein receptor binding domain (RBD) antibody titers decrease significantly with IgA being less affected. Concurrently, neutralizing activity in plasma decreases by five-fold in pseudotype virus assays. In contrast, the number of RBD-specific memory B cells is unchanged. Memory B cells display clonal turnover after 6.2 months, and the antibodies they express have greater somatic hypermutation, increased potency and resistance to RBD mutations, indicative of continued evolution of the humoral response. Analysis of intestinal biopsies obtained from asymptomatic individuals 4 months after coronavirus disease-2019 (COVID-19) onset, using immunofluorescence, or polymerase chain reaction, revealed persistence of SARS-CoV-2 nucleic acids and immunoreactivity in the small bowel of 7 out of 14 volunteers. We conclude that the memory B cell response to SARS-CoV-2 evolves between 1.3 and 6.2 months after infection in a manner that is consistent with antigen persistence.

Competing Interest Statement

The Rockefeller University has filed a provisional patent application in connection with this work on which D.F.R. and M.C.N. are inventors (US patent 63/021,387).

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 January 04, 2021.
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Evolution of Antibody Immunity to SARS-CoV-2
Christian Gaebler, Zijun Wang, Julio C. C. Lorenzi, Frauke Muecksch, Shlomo Finkin, Minami Tokuyama, Alice Cho, Mila Jankovic, Dennis Schaefer-Babajew, Thiago Y. Oliveira, Melissa Cipolla, Charlotte Viant, Christopher O. Barnes, Yaron Bram, Gaëlle Breton, Thomas Hägglöf, Pilar Mendoza, Arlene Hurley, Martina Turroja, Kristie Gordon, Katrina G. Millard, Victor Ramos, Fabian Schmidt, Yiska Weisblum, Divya Jha, Michael Tankelevich, Gustavo Martinez-Delgado, Jim Yee, Roshni Patel, Juan Dizon, Cecille Unson-O’Brien, Irina Shimeliovich, Davide F. Robbiani, Zhen Zhao, Anna Gazumyan, Robert E. Schwartz, Theodora Hatziioannou, Pamela J. Bjorkman, Saurabh Mehandru, Paul D. Bieniasz, Marina Caskey, Michel C. Nussenzweig
bioRxiv 2020.11.03.367391; doi: https://doi.org/10.1101/2020.11.03.367391
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Evolution of Antibody Immunity to SARS-CoV-2
Christian Gaebler, Zijun Wang, Julio C. C. Lorenzi, Frauke Muecksch, Shlomo Finkin, Minami Tokuyama, Alice Cho, Mila Jankovic, Dennis Schaefer-Babajew, Thiago Y. Oliveira, Melissa Cipolla, Charlotte Viant, Christopher O. Barnes, Yaron Bram, Gaëlle Breton, Thomas Hägglöf, Pilar Mendoza, Arlene Hurley, Martina Turroja, Kristie Gordon, Katrina G. Millard, Victor Ramos, Fabian Schmidt, Yiska Weisblum, Divya Jha, Michael Tankelevich, Gustavo Martinez-Delgado, Jim Yee, Roshni Patel, Juan Dizon, Cecille Unson-O’Brien, Irina Shimeliovich, Davide F. Robbiani, Zhen Zhao, Anna Gazumyan, Robert E. Schwartz, Theodora Hatziioannou, Pamela J. Bjorkman, Saurabh Mehandru, Paul D. Bieniasz, Marina Caskey, Michel C. Nussenzweig
bioRxiv 2020.11.03.367391; doi: https://doi.org/10.1101/2020.11.03.367391

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