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

CI Kaku, AJ Bergeron, C Ahlm, J Normark… - Science …, 2022 - science.org
CI Kaku, AJ Bergeron, C Ahlm, J Normark, M Sakharkar, MNE Forsell, LM Walker
Science immunology, 2022science.org
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 …
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.
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