Memory B cell responses to Omicron subvariants after SARS-CoV-2 mRNA breakthrough infection in humans

Zijun Wang, Pengcheng Zhou, Frauke Muecksch, Alice Cho, Tarek Ben Tanfous, Marie Canis, Leander Witte, Brianna Johnson, Raphael Raspe, Fabian Schmidt, Eva Bednarski, Justin Da Silva, Victor Ramos, Shuai Zong, Martina Turroja, Katrina G. Millard, Kai Hui Yao, Irina Shimeliovich, Juan Dizon, Anna KaczynskaMila Jankovic, Anna Gazumyan, Thiago Y. Oliveira, Marina Caskey, Christian Gaebler, Paul D. Bieniasz, Theodora Hatziioannou, Michel C. Nussenzweig

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


Individuals who receive a third mRNA vaccine dose show enhanced protection against severe COVID-19, but little is known about the impact of breakthrough infections on memory responses. Here, we examine the memory antibodies that develop after a third or fourth antigenic exposure by Delta or Omicron BA.1 infection, respectively. A third exposure to antigen by Delta breakthrough increases the number of memory B cells that produce antibodies with comparable potency and breadth to a third mRNA vaccine dose. A fourth antigenic exposure with Omicron BA.1 infection increased variant-specific plasma antibody and memory B cell responses. However, the fourth exposure did not increase the overall frequency of memory B cells or their general potency or breadth compared to a third mRNA vaccine dose. In conclusion, a third antigenic exposure by Delta infection elicits strain-specific memory responses and increases in the overall potency and breadth of the memory B cells. In contrast, the effects of a fourth antigenic exposure with Omicron BA.1 are limited to increased strain-specific memory with little effect on the potency or breadth of memory B cell antibodies. The results suggest that the effect of strain-specific boosting on memory B cell compartment may be limited.
Original languageEnglish (US)
JournalJournal of Experimental Medicine
Issue number12
StatePublished - Dec 1 2022
Externally publishedYes

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Generated from Scopus record by KAUST IRTS on 2023-02-15


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