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

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.