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- Title
Enhanced SARS-CoV-2 humoral immunity following breakthrough infection builds upon the preexisting memory B cell pool.
- Authors
Weber, Timm; Dähling, Sabrina; Rose, Svea; Affeldt, Patrick; Vanshylla, Kanika; Ullrich, Leon; Gieselmann, Lutz; Teipel, Finn; Gruell, Henning; Di Cristanziano, Veronica; Kim, Dae Sung; Georgiou, George; Koch, Manuel; Kreer, Christoph; Klein, Florian
- 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. Editor's summary: As the immune system is exposed to new SARS-CoV-2 variants, it must rapidly adapt, but how repeated antigen contacts influence the evolution of SARS-CoV-2–specific memory B cells is not well defined. Weber et al. explored how third dose SARS-CoV-2 vaccination and subsequent Omicron breakthrough infection influenced antibody and memory B cell responses. Serum antibodies had enhanced neutralization capacity after third dose vaccination. However, the SARS-CoV-2–specific memory B cell pool was significantly expanded only in individuals with a breakthrough infection after third dose. This was due to selection of pre-existing Omicron-neutralizing memory B cells that potently neutralized a broad range of variants that arose after initial vaccination. These findings demonstrate that SARS-CoV-2 immunity is imprinted during early antigen exposure and adapts to new variants. —Hannah Isles
- Subjects
IMMUNOLOGIC memory; BREAKTHROUGH infections; HUMORAL immunity; SARS-CoV-2; BOOSTER vaccines
- Publication
Science Immunology, 2023, Vol 8, Issue 89, p1
- ISSN
2470-9468
- Publication type
Article
- DOI
10.1126/sciimmunol.adk5845