Recall of pre-existing cross-reactive B cell memory following Omicron breakthrough infection

Kaku, C. I.; Bergeron, A. J.; Ahlm, C.; Normark, J.; Sakharkar, M.; Forsell, M. N.; Walker, L. M.

doi:10.1101/2022.04.01.486726

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bioRxiv · 10.1101/2022.04.01.486726

Recall of pre-existing cross-reactive B cell memory following Omicron breakthrough infection

Kaku, C. I.·Bergeron, A. J.·Ahlm, C.·Normark, J.·Sakharkar, M.·Forsell, M. N.·Walker, L. M.

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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.

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Kaku, C. I., Bergeron, A. J., Ahlm, C., Normark, J., Sakharkar, M., Forsell, M. N., Walker, L. M.. 2022-04-01. Recall of pre-existing cross-reactive B cell memory following Omicron breakthrough infection. https://doi.org/10.1101/2022.04.01.486726

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