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

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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 Kaczynska, Mila Jankovic, Anna Gazumyan, Thiago Y Oliveira, Marina Caskey, Christian Gaebler, Paul D Bieniasz, Theodora Hatziioannou, Michel C Nussenzweig

  • J Exp Med
  • 17.579
  • 2022 Dec 5;219(12):e20221006.
  • Human
  • 流式
  • 呼吸系统
  • B细胞
  • 新冠
  • CD27,IgG

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.
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