Increased memory B cell potency and breadth after a SARS-CoV-2 mRNA boost

Frauke Muecksch, Zijun Wang, Alice Cho, Christian Gaebler, Tarek Tanfous, Justin DaSilva, Eva Bednarski, Victor Ramos, Shuai Zong, Brianna Johnson, Raphael Raspe, Dennis Schaefer-Babajew, Irina Shimeliovich, Mridushi Daga, Kai-Hui Yao, Fabian Schmidt, Katrina G. Millard, Martina Turroja, Mila Jankovic, Thiago Y. Oliveira, Anna Gazumyan, Marina Caskey, Theodora Hatziioannou (), Paul D. Bieniasz () and Michel C. Nussenzweig ()
Additional contact information
Frauke Muecksch: The Rockefeller University
Zijun Wang: The Rockefeller University
Alice Cho: The Rockefeller University
Christian Gaebler: The Rockefeller University
Tarek Tanfous: The Rockefeller University
Justin DaSilva: The Rockefeller University
Eva Bednarski: The Rockefeller University
Victor Ramos: The Rockefeller University
Shuai Zong: The Rockefeller University
Brianna Johnson: The Rockefeller University
Raphael Raspe: The Rockefeller University
Dennis Schaefer-Babajew: The Rockefeller University
Irina Shimeliovich: The Rockefeller University
Mridushi Daga: The Rockefeller University
Kai-Hui Yao: The Rockefeller University
Fabian Schmidt: The Rockefeller University
Katrina G. Millard: The Rockefeller University
Martina Turroja: The Rockefeller University
Mila Jankovic: The Rockefeller University
Thiago Y. Oliveira: The Rockefeller University
Anna Gazumyan: The Rockefeller University
Marina Caskey: The Rockefeller University
Theodora Hatziioannou: The Rockefeller University
Paul D. Bieniasz: The Rockefeller University
Michel C. Nussenzweig: The Rockefeller University

Nature, 2022, vol. 607, issue 7917, 128-134

Abstract: Abstract The Omicron variant of SARS-CoV-2 infected many vaccinated and convalescent individuals1–3. Despite the reduced protection from infection, individuals who received three doses of an mRNA vaccine were highly protected from more serious consequences of infection4. Here we examine the memory B cell repertoire in a longitudinal cohort of individuals receiving three mRNA vaccine doses5,6. We find that the third dose is accompanied by an increase in, and evolution of, receptor-binding domain (RBD)-specific memory B cells. The increase is due to expansion of memory B cell clones that were present after the second dose as well as the emergence of new clones. The antibodies encoded by these cells showed significantly increased potency and breadth when compared with antibodies obtained after the second dose. Notably, the increase in potency was especially evident among newly developing clones of memory cells, which differed from persisting clones in targeting more conserved regions of the RBD. Overall, more than 50% of the analysed neutralizing antibodies in the memory compartment after the third mRNA vaccine dose neutralized the Omicron variant. Thus, individuals receiving three doses of an mRNA vaccine have a diverse memory B cell repertoire that can respond rapidly and produce antibodies capable of clearing even diversified variants such as Omicron. These data help to explain why a third dose of a vaccine that was not specifically designed to protect against variants is effective against variant-induced serious disease.

Date: 2022
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DOI: 10.1038/s41586-022-04778-y

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