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

Frauke Muecksch, Zijun Wang, Alice Cho, Christian Gaebler, Tarek Ben 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. OliveiraAnna Gazumyan, Marina Caskey, Theodora Hatziioannou, Paul D. Bieniasz, Michel C. Nussenzweig

Research output: Contribution to journalArticlepeer-review

185 Scopus citations

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.
Original languageEnglish (US)
Pages (from-to)128-134
Number of pages7
JournalNature
Volume607
Issue number7917
DOIs
StatePublished - Jul 7 2022
Externally publishedYes

ASJC Scopus subject areas

  • General

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