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Sci Immunol . Recall of pre-existing cross-reactive B cell memory following Omicron BA.1 breakthrough infection

tetano

Editor, Senior Moderator
Sci Immunol


. 2022 May 12;eabq3511.
doi: 10.1126/sciimmunol.abq3511. Online ahead of print.
Recall of pre-existing cross-reactive B cell memory following Omicron BA.1 breakthrough infection


Chengzi I Kaku[SUP] 1 [/SUP], Alan J Bergeron[SUP] 2 3 [/SUP], Clas Ahlm[SUP] 4 [/SUP], Johan Normark[SUP] 4 [/SUP], Mrunal Sakharkar[SUP] 1 [/SUP], Mattias N E Forsell[SUP] 4 [/SUP], Laura M Walker[SUP] 5 [/SUP]



Affiliations

Abstract

Understanding immune responses following 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 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, 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 pre-existing immunity in shaping the B cell response to heterologous SARS-CoV-2 variant exposure.
 
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