Recall of preexisting cross-reactive B cell memory after Omicron BA.1 breakthrough infection

Sci Immunol. 2022 Jul 29;7(73):eabq3511. doi: 10.1126/sciimmunol.abq3511. Epub 2022 Jul 29.

Abstract

Understanding immune responses after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) breakthrough infection will facilitate the development of next-generation vaccines. Here, we profiled spike (S)-specific B cell responses after Omicron/BA.1 infection in messenger RNA-vaccinated donors. The acute antibody response was characterized by high levels of somatic hypermutation and a bias toward recognition of ancestral SARS-CoV-2 strains, suggesting the early activation of vaccine-induced memory B cells. BA.1 breakthrough infection induced a shift in B cell immunodominance hierarchy from the S2 subunit, which is highly conserved across SARS-CoV-2 variants of concern (VOCs), and toward the antigenically variable receptor binding domain (RBD). A large proportion of RBD-directed neutralizing antibodies isolated from BA.1 breakthrough infection donors displayed convergent sequence features and broadly recognized SARS-CoV-2 VOCs. Together, these findings provide insights into the role of preexisting immunity in shaping the B cell response to heterologous SARS-CoV-2 variant exposure.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Viral
  • B-Lymphocytes* / immunology
  • COVID-19 Vaccines / immunology
  • COVID-19* / immunology
  • Cross Reactions
  • Humans
  • Immunologic Memory*
  • Membrane Glycoproteins
  • SARS-CoV-2
  • Spike Glycoprotein, Coronavirus / genetics
  • Viral Envelope Proteins

Substances

  • Antibodies, Viral
  • COVID-19 Vaccines
  • Membrane Glycoproteins
  • Spike Glycoprotein, Coronavirus
  • Viral Envelope Proteins
  • spike protein, SARS-CoV-2

Supplementary concepts

  • SARS-CoV-2 variants