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, Víctor Ramos, Shuai Zong, Martina Turroja, Katrina G. Millard, Kai-Hui Yao, Irina Shimeliovich, Juan Dizon, Anna Kaczynska, Mila Janković, Anna Gazumyan, Thiago Y. Oliveira, Marina Caskey, Christian Gaebler, Paul D. Bieniasz, Théodora Hatziioannou, Michel C. Nussenzweig
Abstract
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.