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Temporal and transcriptional programming of effector memory B cells shapes vaccine platform-dependent humoral immunity
Anoma Nellore (University of Alabama at Birmingham, NYU Langone Health), Christopher Fucile (University of Alabama at Birmingham), Christopher D. Scharer (Emory University), Page Murray (NYU Langone Health, New York University), Jack T. Geer (University of Alabama at Birmingham, UAB Medicine), Jacey Lemonds (University of Alabama at Birmingham, UAB Medicine), Betty J. Mousseau (University of Alabama at Birmingham, UAB Medicine), Fen Zhou (University of Alabama at Birmingham, UAB Medicine), Esther Zumaquero (University of Alabama at Birmingham, UAB Medicine), Jobaida Akhter (University of Alabama at Birmingham), Ellie Ivanova (NYU Langone Health, New York University), V. Estrada-Navarro (NYU Langone Health, New York University), Paul Goepfert (University of Alabama at Birmingham, UAB Medicine), Ralf Duerr (NYU Langone Health, New York University), Ramin S. Herati (NYU Langone Health, New York University), Alexander D. Rosenberg (University of Alabama at Birmingham), Frances E. Lund (University of Alabama at Birmingham, UAB Medicine), Troy D. Randall (University of Alabama at Birmingham)
Abstract: 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.