Receptor-Binding-Domain-Specific B Cell Responses Induced by mRNA Immunization against SARS-CoV-2. 2023

Maria Geropeppa, and Ioanna Papadatou, and Panagiotis Sarantis, and Marianna Tzanoudaki, and Ioannis Ntanasis-Stathopoulos, and Tina Bagratuni, and Evangelos Terpos, and Vana Spoulou
Immunobiology and Vaccinology Research Laboratory, School of Medicine, National and Kapodistrian University of Athens, 11527 Athens, Greece.

mRNA vaccines have been instrumental in controlling the SARS-CoV-2 pandemic, but the short-lived protection mediated by Receptor Binding Domain (RBD)-specific antibodies necessitates frequent revaccinations to enhance vaccine-induced immunity. The development of RBD-specific B cell memory is critical for improving the qualitative and quantitative characteristics of the immune response. However, the effect of additional doses of mRNA vaccines on the composition of the RBD-specific B cell memory pool remains unclear. In this study, we found that dual BNT162b2 vaccination significantly increased both total RBD-specific and memory RBD-specific B cells and neutralizing antibodies. Following the second BNT162b2 dose, we showed a trend for the enrichment of CD27+IgM- memory RBD-specific B cells, which are known to correlate with a strong humoral response upon re-challenge. Repeated Measures Correlation (rmcorr) analysis revealed a significant correlation between antibody titers and both total and memory RBD-specific B cells, demonstrating that B cell and antibody responses are generated in a coordinated manner following BNT162b2 mRNA immunization. Our findings indicate that additional doses of the BNT162b2 mRNA vaccine enhance the qualitative and quantitative enrichment of the memory B cell pool against the vaccine antigens and collectively demonstrate the induction of a coordinated immune response to mRNA vaccination.

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