Temporal and transcriptional programming of effector memory B cells shapes vaccine platform-dependent humoral immunity.

This study investigates how influenza vaccine platform shapes the memory B cell responses that underlie durable antibody protection. Using fluorescent hemagglutinin (HA) probes, the authors compared HA-specific IgD-negative B cells in adults who received either live attenuated influenza vaccine (LAIV) or inactivated influenza vaccine (IIV). Both platforms induced circulating T-bet+ HA+ B cells with similar phenotypic features, but their relationship to antibody outcomes diverged sharply: while these cells track with durable IgG responses after IIV, only early (day 7-14) T-bet+ HA+ B cell frequencies predicted durable IgA responses after LAIV. Single-cell transcriptional profiling further revealed that LAIV and IIV elicit distinct effector-memory B cell states, including an LAIV-enriched, terminally differentiated TBX21/ZEB2-high population with limited plasmablast recall potential. Together, these findings show that influenza vaccination drives platform-dependent diversification of HA-specific B cell states, highlighting the need for vaccine-platform-specific correlates of immune protection.