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Recall of pre-existing cross-reactive B cell memory following Omicron breakthrough infection
Chengzi I Kaku; Alan J Bergeron; Clas Ahlm; Johan Normark; Mrunal Sakharkar; Mattias NE Forsell; Laura M Walker.
Afiliación
  • Chengzi I Kaku; Adimab, LLC
  • Alan J Bergeron; Norris Cotton Cancer Center, Dartmouth Hitchcock Medical Center; Department of Microbiology and Immunology, Dartmouth College
  • Clas Ahlm; Umea University
  • Johan Normark; Umea University
  • Mrunal Sakharkar; Adimab LLC
  • Mattias NE Forsell; Umea University
  • Laura M Walker; Adagio Therapeutics, Inc; Adimab, LLC
Preprint en En | PREPRINT-BIORXIV | ID: ppbiorxiv-486726
ABSTRACT
Understanding immune responses following SARS-CoV-2 breakthrough infection will facilitate the development of next-generation vaccines. Here, we profiled spike (S)-specific B cell responses following Omicron/BA.1 infection in mRNA-vaccinated donors. The acute antibody response was characterized by high levels of somatic hypermutation (SHM) and a bias toward recognition of ancestral SARS-CoV-2 strains, suggesting the early activation of vaccine-induced memory B cells (MBCs). BA.1 breakthrough infection induced a shift in B cell immunodominance hierarchy from the S2 subunit toward the 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 variants of concern (VOCs). Together, these findings provide fundamental insights into the role of pre-existing immunity in shaping the B cell response to heterologous SARS-CoV-2 variant exposure. One sentence summaryBA.1 breakthrough infection activates pre-existing memory B cells with broad activity against SARS-CoV-2 variants.
Licencia
cc_by_nc_nd
Texto completo: 1 Colección: 09-preprints Base de datos: PREPRINT-BIORXIV Tipo de estudio: Rct Idioma: En Año: 2022 Tipo del documento: Preprint
Texto completo: 1 Colección: 09-preprints Base de datos: PREPRINT-BIORXIV Tipo de estudio: Rct Idioma: En Año: 2022 Tipo del documento: Preprint