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Vaccination boosts naturally enhanced neutralizing breadth to SARS-CoV-2 one year after infection

Zijun Wang, Frauke Muecksch, Dennis Schaefer-Babajew, Shlomo Finkin, Charlotte Viant, Christian Gaebler, Christopher Barnes, Melissa Cipolla, Victor Ramos, Thiago Y. Oliveira, Alice Cho, Fabian Schmidt, Justin da Silva, Eva Bednarski, Mridushi Daga, Martina Turroja, Katrina G. Millard, Mila Jankovic, Anna Gazumyan, Paul D. Bieniasz, Marina Caskey, Theodora Hatziioannou, Michel C. Nussenzweig
doi: https://doi.org/10.1101/2021.05.07.443175
Zijun Wang
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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Dennis Schaefer-Babajew
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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Charlotte Viant
1Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA
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Christian Gaebler
1Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA
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Christopher Barnes
3Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA
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Melissa Cipolla
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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Thiago Y. Oliveira
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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Fabian Schmidt
2Laboratory of Retrovirology, The Rockefeller University, New York, NY 10065, USA
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Justin da Silva
2Laboratory of Retrovirology, The Rockefeller University, New York, NY 10065, USA
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Eva Bednarski
2Laboratory of Retrovirology, The Rockefeller University, New York, NY 10065, USA
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Mridushi Daga
1Laboratory of Molecular Immunology, 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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Katrina G. Millard
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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Anna Gazumyan
1Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA
4Howard Hughes Medical Institute
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Paul D. Bieniasz
2Laboratory of Retrovirology, The Rockefeller University, New York, NY 10065, USA
4Howard Hughes Medical Institute
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  • For correspondence: pbieniasz@rockefeller.edu mcaskey@rockefeller.edu thatziio@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: pbieniasz@rockefeller.edu mcaskey@rockefeller.edu thatziio@rockefeller.edu nussen@rockefeller.edu
Theodora Hatziioannou
2Laboratory of Retrovirology, The Rockefeller University, New York, NY 10065, USA
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  • For correspondence: pbieniasz@rockefeller.edu mcaskey@rockefeller.edu thatziio@rockefeller.edu nussen@rockefeller.edu
Michel C. Nussenzweig
1Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA
4Howard Hughes Medical Institute
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  • For correspondence: pbieniasz@rockefeller.edu mcaskey@rockefeller.edu thatziio@rockefeller.edu nussen@rockefeller.edu
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Abstract

Over one year after its inception, the coronavirus disease-2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) remains difficult to control despite the availability of several excellent vaccines. Progress in controlling the pandemic is slowed by the emergence of variants that appear to be more transmissible and more resistant to antibodies1,2. Here we report on a cohort of 63 COVID-19-convalescent individuals assessed at 1.3, 6.2 and 12 months after infection, 41% of whom also received mRNA vaccines3,4. In the absence of vaccination antibody reactivity to the receptor binding domain (RBD) of SARS-CoV-2, neutralizing activity and the number of RBD-specific memory B cells remain relatively stable from 6 to 12 months. Vaccination increases all components of the humoral response, and as expected, results in serum neutralizing activities against variants of concern that are comparable to or greater than neutralizing activity against the original Wuhan Hu-1 achieved by vaccination of naïve individuals2,5–8. The mechanism underlying these broad-based responses involves ongoing antibody somatic mutation, memory B cell clonal turnover, and development of monoclonal antibodies that are exceptionally resistant to SARS-CoV-2 RBD mutations, including those found in variants of concern4,9. In addition, B cell clones expressing broad and potent antibodies are selectively retained in the repertoire over time and expand dramatically after vaccination. The data suggest that immunity in convalescent individuals will be very long lasting and that convalescent individuals who receive available mRNA vaccines will produce antibodies and memory B cells that should be protective against circulating SARS-CoV-2 variants. Should memory responses evolve in a similar manner in vaccinated individuals, additional appropriately timed boosting with available vaccines could cover most circulating variants of concern.

Competing Interest Statement

The Rockefeller University has filed a provisional patent application in connection with this work on which M.C.N.is an inventor (US patent 63/021,387). The patent has been licensed by Rockefeller University to Bristol Meyers Squib.

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 May 09, 2021.
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Vaccination boosts naturally enhanced neutralizing breadth to SARS-CoV-2 one year after infection
Zijun Wang, Frauke Muecksch, Dennis Schaefer-Babajew, Shlomo Finkin, Charlotte Viant, Christian Gaebler, Christopher Barnes, Melissa Cipolla, Victor Ramos, Thiago Y. Oliveira, Alice Cho, Fabian Schmidt, Justin da Silva, Eva Bednarski, Mridushi Daga, Martina Turroja, Katrina G. Millard, Mila Jankovic, Anna Gazumyan, Paul D. Bieniasz, Marina Caskey, Theodora Hatziioannou, Michel C. Nussenzweig
bioRxiv 2021.05.07.443175; doi: https://doi.org/10.1101/2021.05.07.443175
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Vaccination boosts naturally enhanced neutralizing breadth to SARS-CoV-2 one year after infection
Zijun Wang, Frauke Muecksch, Dennis Schaefer-Babajew, Shlomo Finkin, Charlotte Viant, Christian Gaebler, Christopher Barnes, Melissa Cipolla, Victor Ramos, Thiago Y. Oliveira, Alice Cho, Fabian Schmidt, Justin da Silva, Eva Bednarski, Mridushi Daga, Martina Turroja, Katrina G. Millard, Mila Jankovic, Anna Gazumyan, Paul D. Bieniasz, Marina Caskey, Theodora Hatziioannou, Michel C. Nussenzweig
bioRxiv 2021.05.07.443175; doi: https://doi.org/10.1101/2021.05.07.443175

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