Enhanced SARS-CoV-2 humoral immunity following breakthrough infection builds upon the preexisting memory B cell pool
Timm Weber, Sabrina Dähling, S. Rose, Patrick Affeldt, Kanika Vanshylla, Leon Ullrich, Lutz Gieselmann, Finn Teipel, Henning Gruell, Veronica Di Cristanziano, Dae Sung Kim, George Georgiou, Manuel Koch, Christoph Kreer, Florian Klein
Abstract
The human immune response must continuously adapt to newly emerging SARS-CoV-2 variants. To investigate how B cells respond to repeated SARS-CoV-2 antigen exposure by Wu01 booster vaccination and Omicron breakthrough infection, we performed a molecular longitudinal analysis of the memory B cell pool. We demonstrate that a subsequent breakthrough infection substantially increases the frequency of B cells encoding SARS-CoV-2-neutralizing antibodies. However, this is not primarily attributable to maturation, but to selection of preexisting B cell clones. Moreover, broadly reactive memory B cells arose early and even neutralized highly mutated variants like XBB.1.5 that the individuals had not encountered. Together, our data show that SARS-CoV-2 immunity is largely imprinted on Wu01 over the course of multiple antigen contacts but can respond to new variants through preexisting diversity.