mRNA-based influenza vaccine expands the B cell response breadth in humans

Abstract: 

"Conventional influenza virus vaccines induce antibody responses of limited breadth. Whether mRNA-based influenza virus vaccines can induce a superior germinal center (GC) response in humans remains unclear. Here we assessed B cell responses in an observational study of cohorts of healthy young adults receiving a licensed, split-virion or investigative mRNA-based quadrivalent seasonal influenza virus vaccine over two consecutive seasons. mRNA-based vaccines consistently elicited higher antibody titers and frequencies of memory B cells. In the draining lymph nodes, mRNA vaccination stimulated sustained GC reactions that persisted for at least 26 weeks after vaccination in 5 of 13 participants across the two seasons. Proteomic analysis of serum IgG repertoire showed that mRNA vaccination increased the number of vaccine-elicited serum IgG clonotypes and promoted intraclonal expansion within pre-existing clonotypes. B cell lineage analyses further indicated that expanded serum clonotypes map to GC B cell-associated sub-branches, consistent with ongoing GC-driven evolution underlying intraclonal expansion. This repertoire remodeling was accompanied by increased binding breadth against antigenically divergent influenza viruses. These findings reveal a key role for persistent GC responses in broadening the repertoire of vaccine-induced antibodies."

Matz, H.C., Yu, T.G., Dixit, K., Kikawa, C., Zhou, J.Q., Pena Alzua, G., Peyton, L., Madsen, A., Han, F., Farrell, A.G., Hoelzl, R., Schmitz, A.J., Horvath, S.C., Keplinger, H.K., Strnad, B.S., Hoegger, M.J., Middleton, W.D., Klebert, M.K., Lin, N.H., Nachbagauer, R., Krammer, F., Paris, R., Bloom, J.D., Turner, J.S., Presti, R.M., Lee, J., and Ellebedy, A.H. (2026). mRNA-based influenza vaccine expands the B cell response breadth in humans. Nature Immunology.