Diverse priming outcomes under conditions of very rare precursor B cells

Rare naive B cells can have special pathogen-recognition features giving them the potential to make outsized contributions to protective immunity. However, they infrequently participate in immune responses. We investigated how germline-targeting vaccine delivery and adjuvant selection affect priming of exceptionally rare BG18-like HIV broadly neutralizing antibody-precursor B cells (50% of animals. One group had vaccine-specific GC responses equivalent to ED+SMNP, but scarce BG18-like memory B cells. Following homologous boosting, BG18-like memory B cells were more frequent in a bolus priming group, but had lower somatic hypermutation and affinities. This outcome was inversely associated with post-prime antibody titers, suggesting antibody feedback significantly influences rare precursor B cell responses.