tetano
Editor, Senior Moderator
Nat Immunol
. 2026 Jun 15.
doi: 10.1038/s41590-026-02569-5. Online ahead of print.
mRNA-based influenza vaccine expands the B cell response breadth in humans
Hanover C Matz[SUP] #[/SUP][SUP] 1 [/SUP], Tae-Geun Yu[SUP] #[/SUP][SUP] 2 [/SUP], Kritika Dixit[SUP] 1 [/SUP], Caroline Kikawa[SUP] 3 [/SUP], Julian Q Zhou[SUP] 1 [/SUP], Garazi Pena Alzua[SUP] 4 5 [/SUP], Lowrey Peyton[SUP] 2 6 [/SUP], Anders Madsen[SUP] 7 8 [/SUP], Fangjie Han[SUP] 1 [/SUP], Ariana Ghez Farrell[SUP] 9 [/SUP], Robert Hoelzl[SUP] 4 [/SUP], Aaron J Schmitz[SUP] 1 [/SUP], Stephen C Horvath[SUP] 1 [/SUP], Hunter K Keplinger[SUP] 1 [/SUP], Benjamin S Strnad[SUP] 10 [/SUP], Mark J Hoegger[SUP] 10 [/SUP], William D Middleton[SUP] 10 [/SUP], Michael K Klebert[SUP] 11 [/SUP], Nina H Lin[SUP] 12 [/SUP], Raffael Nachbagauer[SUP] 12 [/SUP], Florian Krammer[SUP] 4 5 13 14 15 [/SUP], Robert Paris[SUP] 12 [/SUP], Jesse D Bloom[SUP] 16 17 [/SUP], Jackson S Turner[SUP] 1 [/SUP], Rachel M Presti[SUP] 11 18 19 20 [/SUP], Jiwon Lee[SUP] 21 22 23 [/SUP], Ali H Ellebedy[SUP] 24 25 26 [/SUP]
Affiliations
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.
. 2026 Jun 15.
doi: 10.1038/s41590-026-02569-5. Online ahead of print.
mRNA-based influenza vaccine expands the B cell response breadth in humans
Hanover C Matz[SUP] #[/SUP][SUP] 1 [/SUP], Tae-Geun Yu[SUP] #[/SUP][SUP] 2 [/SUP], Kritika Dixit[SUP] 1 [/SUP], Caroline Kikawa[SUP] 3 [/SUP], Julian Q Zhou[SUP] 1 [/SUP], Garazi Pena Alzua[SUP] 4 5 [/SUP], Lowrey Peyton[SUP] 2 6 [/SUP], Anders Madsen[SUP] 7 8 [/SUP], Fangjie Han[SUP] 1 [/SUP], Ariana Ghez Farrell[SUP] 9 [/SUP], Robert Hoelzl[SUP] 4 [/SUP], Aaron J Schmitz[SUP] 1 [/SUP], Stephen C Horvath[SUP] 1 [/SUP], Hunter K Keplinger[SUP] 1 [/SUP], Benjamin S Strnad[SUP] 10 [/SUP], Mark J Hoegger[SUP] 10 [/SUP], William D Middleton[SUP] 10 [/SUP], Michael K Klebert[SUP] 11 [/SUP], Nina H Lin[SUP] 12 [/SUP], Raffael Nachbagauer[SUP] 12 [/SUP], Florian Krammer[SUP] 4 5 13 14 15 [/SUP], Robert Paris[SUP] 12 [/SUP], Jesse D Bloom[SUP] 16 17 [/SUP], Jackson S Turner[SUP] 1 [/SUP], Rachel M Presti[SUP] 11 18 19 20 [/SUP], Jiwon Lee[SUP] 21 22 23 [/SUP], Ali H Ellebedy[SUP] 24 25 26 [/SUP]
Affiliations
- PMID: 42297975
- DOI: 10.1038/s41590-026-02569-5
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.