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mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants

Zijun Wang, Fabian Schmidt, Yiska Weisblum, Frauke Muecksch, Christopher O. Barnes, Shlomo Finkin, Dennis Schaefer-Babajew, Melissa Cipolla, Christian Gaebler, Jenna A. Lieberman, Thiago Y. Oliveira, Zhi Yang, Morgan E. Abernathy, Kathryn E. Huey-Tubman, Arlene Hurley, Martina Turroja, Kamille A. West, Kristie Gordon, Katrina G. Millard, Victor Ramos, Justin Da Silva, Jianliang Xu, Robert A. Colbert, Roshni Patel, Juan Dizon, Cecille Unson-O’Brien, Irina Shimeliovich, Anna Gazumyan, Marina Caskey, Pamela J. Bjorkman, Rafael Casellas, Theodora Hatziioannou, Paul D. Bieniasz, Michel C. Nussenzweig
doi: https://doi.org/10.1101/2021.01.15.426911
Zijun Wang
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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Frauke Muecksch
2Laboratory of Retrovirology, The Rockefeller University, New York, NY 10065, USA
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Christopher O. Barnes
3Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA
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Shlomo Finkin
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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Melissa Cipolla
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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Jenna A. Lieberman
4Lymphocyte Nuclear Biology, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892.
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Thiago Y. Oliveira
1Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA
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Zhi Yang
3Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA
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Morgan E. Abernathy
3Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA
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Kathryn E. Huey-Tubman
3Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA
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Arlene Hurley
5Hospital 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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Kamille A. West
6Department of Transfusion Medicine, National Institutes of Health Clinical Center, Bethesda, MD 20892.
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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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Justin Da Silva
2Laboratory of Retrovirology, The Rockefeller University, New York, NY 10065, USA
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Jianliang Xu
4Lymphocyte Nuclear Biology, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892.
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Robert A. Colbert
7Pediatric Translational Research Branch and Office of the Clinical Director, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892.
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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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Anna Gazumyan
1Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA
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Marina Caskey
1Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA
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Pamela J. Bjorkman
3Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA
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  • For correspondence: pbieniasz@rockefeller.edu bjorkman@caltech.edu rafael.casellas@nih.gov thatziio@rockefeller.edu nussen@rockefeller.edu
Rafael Casellas
4Lymphocyte Nuclear Biology, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892.
8The NIH Regulome Project, National Institutes of Health, Bethesda, MD 20892.
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  • For correspondence: pbieniasz@rockefeller.edu bjorkman@caltech.edu rafael.casellas@nih.gov 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 bjorkman@caltech.edu rafael.casellas@nih.gov thatziio@rockefeller.edu nussen@rockefeller.edu
Paul D. Bieniasz
2Laboratory of Retrovirology, The Rockefeller University, New York, NY 10065, USA
9Howard Hughes Medical Institute
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  • For correspondence: pbieniasz@rockefeller.edu bjorkman@caltech.edu rafael.casellas@nih.gov thatziio@rockefeller.edu nussen@rockefeller.edu
Michel C. Nussenzweig
1Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA
9Howard Hughes Medical Institute
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  • For correspondence: pbieniasz@rockefeller.edu bjorkman@caltech.edu rafael.casellas@nih.gov thatziio@rockefeller.edu nussen@rockefeller.edu
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Abstract

To date severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has infected over 100 million individuals resulting in over two million deaths. Many vaccines are being deployed to prevent coronavirus disease 2019 (COVID-19) including two novel mRNA-based vaccines1,2. These vaccines elicit neutralizing antibodies and appear to be safe and effective, but the precise nature of the elicited antibodies is not known3–6. Here we report on the antibody and memory B cell responses in a cohort of 20 volunteers who received either the Moderna (mRNA-1273) or Pfizer-BioNTech (BNT162b2) vaccines. Consistent with prior reports, 8 weeks after the second vaccine injection volunteers showed high levels of IgM, and IgG anti-SARS-CoV-2 spike protein (S) and receptor binding domain (RBD) binding titers3,5,6. Moreover, the plasma neutralizing activity, and the relative numbers of RBD-specific memory B cells were equivalent to individuals who recovered from natural infection7,8. However, activity against SARS-CoV-2 variants encoding E484K or N501Y or the K417N:E484K:N501Y combination was reduced by a small but significant margin. Consistent with these findings, vaccine-elicited monoclonal antibodies (mAbs) potently neutralize SARS-CoV-2, targeting a number of different RBD epitopes in common with mAbs isolated from infected donors. Structural analyses of mAbs complexed with S trimer suggest that vaccine- and virus-encoded S adopts similar conformations to induce equivalent anti-RBD antibodies. However, neutralization by 14 of the 17 most potent mAbs tested was reduced or abolished by either K417N, or E484K, or N501Y mutations. Notably, the same mutations were selected when recombinant vesicular stomatitis virus (rVSV)/SARS-CoV-2 S was cultured in the presence of the vaccine elicited mAbs. Taken together the results suggest that the monoclonal antibodies in clinical use should be tested against newly arising variants, and that mRNA vaccines may need to be updated periodically to avoid potential loss of clinical efficacy.

Competing Interest Statement

The Rockefeller University has filed a provisional patent application in connection with this work on which Z.W. and M.C.N. are inventors (US patent 63/199,676).

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 30, 2021.
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mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants
Zijun Wang, Fabian Schmidt, Yiska Weisblum, Frauke Muecksch, Christopher O. Barnes, Shlomo Finkin, Dennis Schaefer-Babajew, Melissa Cipolla, Christian Gaebler, Jenna A. Lieberman, Thiago Y. Oliveira, Zhi Yang, Morgan E. Abernathy, Kathryn E. Huey-Tubman, Arlene Hurley, Martina Turroja, Kamille A. West, Kristie Gordon, Katrina G. Millard, Victor Ramos, Justin Da Silva, Jianliang Xu, Robert A. Colbert, Roshni Patel, Juan Dizon, Cecille Unson-O’Brien, Irina Shimeliovich, Anna Gazumyan, Marina Caskey, Pamela J. Bjorkman, Rafael Casellas, Theodora Hatziioannou, Paul D. Bieniasz, Michel C. Nussenzweig
bioRxiv 2021.01.15.426911; doi: https://doi.org/10.1101/2021.01.15.426911
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mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants
Zijun Wang, Fabian Schmidt, Yiska Weisblum, Frauke Muecksch, Christopher O. Barnes, Shlomo Finkin, Dennis Schaefer-Babajew, Melissa Cipolla, Christian Gaebler, Jenna A. Lieberman, Thiago Y. Oliveira, Zhi Yang, Morgan E. Abernathy, Kathryn E. Huey-Tubman, Arlene Hurley, Martina Turroja, Kamille A. West, Kristie Gordon, Katrina G. Millard, Victor Ramos, Justin Da Silva, Jianliang Xu, Robert A. Colbert, Roshni Patel, Juan Dizon, Cecille Unson-O’Brien, Irina Shimeliovich, Anna Gazumyan, Marina Caskey, Pamela J. Bjorkman, Rafael Casellas, Theodora Hatziioannou, Paul D. Bieniasz, Michel C. Nussenzweig
bioRxiv 2021.01.15.426911; doi: https://doi.org/10.1101/2021.01.15.426911

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