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 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 () and Michel C. Nussenzweig ()
Additional contact information
Zijun Wang: The Rockefeller University
Fabian Schmidt: The Rockefeller University
Yiska Weisblum: The Rockefeller University
Frauke Muecksch: The Rockefeller University
Christopher O. Barnes: California Institute of Technology
Shlomo Finkin: The Rockefeller University
Dennis Schaefer-Babajew: The Rockefeller University
Melissa Cipolla: The Rockefeller University
Christian Gaebler: The Rockefeller University
Jenna A. Lieberman: National Institutes of Health
Thiago Y. Oliveira: The Rockefeller University
Zhi Yang: California Institute of Technology
Morgan E. Abernathy: California Institute of Technology
Kathryn E. Huey-Tubman: California Institute of Technology
Arlene Hurley: The Rockefeller University
Martina Turroja: The Rockefeller University
Kamille A. West: National Institutes of Health Clinical Center
Kristie Gordon: The Rockefeller University
Katrina G. Millard: The Rockefeller University
Victor Ramos: The Rockefeller University
Justin Silva: The Rockefeller University
Jianliang Xu: National Institutes of Health
Robert A. Colbert: National Institutes of Health
Roshni Patel: The Rockefeller University
Juan Dizon: The Rockefeller University
Cecille Unson-O’Brien: The Rockefeller University
Irina Shimeliovich: The Rockefeller University
Anna Gazumyan: The Rockefeller University
Marina Caskey: The Rockefeller University
Pamela J. Bjorkman: California Institute of Technology
Rafael Casellas: National Institutes of Health
Theodora Hatziioannou: The Rockefeller University
Paul D. Bieniasz: The Rockefeller University
Michel C. Nussenzweig: The Rockefeller University

Nature, 2021, vol. 592, issue 7855, 616-622

Abstract: Abstract Here we report on the antibody and memory B cell responses of a cohort of 20 volunteers who received the Moderna (mRNA-1273) or Pfizer–BioNTech (BNT162b2) vaccine against SARS-CoV-21–4. Eight weeks after the second injection of vaccine, volunteers showed high levels of IgM and IgG anti-SARS-CoV-2 spike protein (S) and receptor-binding-domain (RBD) binding titre. Moreover, the plasma neutralizing activity and relative numbers of RBD-specific memory B cells of vaccinated volunteers were equivalent to those of individuals who had recovered from natural infection5,6. However, activity against SARS-CoV-2 variants that encode E484K-, N501Y- or K417N/E484K/N501-mutant S was reduced by a small—but significant—margin. The monoclonal antibodies elicited by the vaccines potently neutralize SARS-CoV-2, and target a number of different RBD epitopes in common with monoclonal antibodies isolated from infected donors5–8. However, neutralization by 14 of the 17 most-potent monoclonal antibodies that we tested was reduced or abolished by the K417N, E484K or N501Y mutation. Notably, these mutations were selected when we cultured recombinant vesicular stomatitis virus expressing SARS-CoV-2 S in the presence of the monoclonal antibodies elicited by the vaccines. Together, these 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 a potential loss of clinical efficacy.

Date: 2021
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DOI: 10.1038/s41586-021-03324-6

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