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<p>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月15日

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  • Hanover C. Matz,
  • Tae-Geun Yu,
  • Kritika Dixit,
  • Caroline Kikawa,
  • Julian Q. Zhou,
  • Garazi Pena Alzua,
  • Lowrey Peyton,
  • Anders Madsen,
  • Fangjie Han,
  • Ariana Ghez Farrell,
  • Robert Hoelzl,
  • Aaron J. Schmitz,
  • Stephen C. Horvath,
  • Hunter K. Keplinger,
  • Benjamin S. Strnad,
  • Mark J. Hoegger,
  • William D. Middleton,
  • Michael K. Klebert,
  • Nina H. Lin,
  • Raffael Nachbagauer,
  • Florian Krammer,
  • Robert Paris,
  • Jesse D. Bloom,
  • Jackson S. Turner,
  • Rachel M. Presti,
  • Jiwon Lee,
  • Ali H. Ellebedy

摘要

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.