Enhanced SARS-CoV-2 humoral immunity following breakthrough infection builds upon the preexisting memory B cell pool

Sci Immunol. 2023 Nov 17;8(89):eadk5845. doi: 10.1126/sciimmunol.adk5845. Epub 2023 Nov 17.

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.

MeSH terms

  • Antibodies, Viral
  • Breakthrough Infections
  • COVID-19*
  • Humans
  • Immunity, Humoral
  • Memory B Cells*
  • SARS-CoV-2

Substances

  • Antibodies, Viral

Supplementary concepts

  • SARS-CoV-2 variants