{
  "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. This study compares the humoral response of individuals who received inactivated influenza vaccines to that of individuals who received an mRNA-based quadrivalent influenza vaccine. The mRNA-based vaccine induced prolonged germinal center responses, more antibodies and increased numbers of memory B cells.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA",
    "Thayer School of Engineering, Dartmouth College, Hanover, NH, USA",
    "Department of Genome Sciences, Medical Scientist Training Program, University of Washington, Seattle, WA, USA",
    "Center for Vaccine Research and Pandemic Preparedness (C-VaRPP), Icahn School of Medicine at Mount Sinai, New York, NY, USA",
    "Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA",
    "Department of Biomedical Data Science, Geisel School of Medicine at Dartmouth, Hanover, NH, USA",
    "Department of Microbiology, Haukeland University Hospital, Bergen, Norway",
    "Influenza Centre, Department of Clinical Science, University of Bergen, Bergen, Norway",
    "Molecular and Cellular Biology Graduate Program, University of Washington, Seattle, WA, USA",
    "Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO, USA",
    "Infectious Disease Clinical Research Unit, Washington University School of Medicine, St. Louis, MO, USA",
    "Moderna, Cambridge, MA, USA",
    "Department of Pathology, Molecular and Cell Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA",
    "Ignaz Semmelweis Institute, Interuniversity Institute for Infection Research, Medical University of Vienna, Vienna, Austria",
    "Ludwig Boltzmann Institute for Science Outreach and Pandemic Preparedness at the Medical University of Vienna, Medical University of Vienna, Vienna, Austria",
    "Fred Hutch Cancer Center, Seattle, WA, USA",
    "Howard Hughes Medical Institute, Seattle, WA, USA",
    "Center for Vaccines and Immunity to Microbial Pathogens, Washington University School of Medicine, St. Louis, MO, USA",
    "Division of Infectious Diseases, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO, USA",
    "The Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO, USA",
    "Department of Convergence Medicine, Korea University College of Medicine, Seoul, Republic of Korea. jiwonjlee@korea.ac.kr",
    "Thayer School of Engineering, Dartmouth College, Hanover, NH, USA. jiwonjlee@korea.ac.kr",
    "Vaccine Innovation Center, Korea University College of Medicine, Seoul, Republic of Korea. jiwonjlee@korea.ac.kr",
    "Center for Vaccines and Immunity to Microbial Pathogens, Washington University School of Medicine, St. Louis, MO, USA. ellebedy@wustl.edu",
    "Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA. ellebedy@wustl.edu",
    "The Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO, USA. ellebedy@wustl.edu"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 27,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Hanover C. Matz",
      "orcid": "0000-0002-0669-1696"
    },
    {
      "affs": [
        1
      ],
      "name": "Tae-Geun Yu"
    },
    {
      "affs": [
        0
      ],
      "name": "Kritika Dixit"
    },
    {
      "affs": [
        2
      ],
      "name": "Caroline Kikawa",
      "orcid": "0000-0002-8654-5663"
    },
    {
      "affs": [
        0
      ],
      "name": "Julian Q. Zhou",
      "orcid": "0000-0001-9602-2092"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Garazi Peña Alzua",
      "orcid": "0000-0001-9139-9915"
    },
    {
      "affs": [
        5,
        1
      ],
      "name": "Lowrey Peyton",
      "orcid": "0009-0004-0933-758X"
    },
    {
      "affs": [
        6,
        7
      ],
      "name": "Anders Madsen",
      "orcid": "0000-0002-0626-5443"
    },
    {
      "affs": [
        0
      ],
      "name": "Fangjie Han"
    },
    {
      "affs": [
        8
      ],
      "name": "Ariana Ghez Farrell",
      "orcid": "0000-0002-1389-0992"
    },
    {
      "affs": [
        4
      ],
      "name": "Robert Hoelzl",
      "orcid": "0009-0009-2536-8219"
    },
    {
      "affs": [
        0
      ],
      "name": "Aaron J. Schmitz",
      "orcid": "0000-0002-8077-6751"
    },
    {
      "affs": [
        0
      ],
      "name": "Stephen C. Horvath",
      "orcid": "0000-0001-5324-1666"
    },
    {
      "affs": [
        0
      ],
      "name": "Hunter K. Keplinger"
    },
    {
      "affs": [
        9
      ],
      "name": "Benjamin S. Strnad",
      "orcid": "0000-0003-2308-1299"
    },
    {
      "affs": [
        9
      ],
      "name": "Mark Jeffrey Hoegger",
      "orcid": "0000-0002-8214-8177"
    },
    {
      "affs": [
        9
      ],
      "name": "William Dana Middleton",
      "orcid": "0000-0002-9869-1107"
    },
    {
      "affs": [
        10
      ],
      "name": "Michael K. Klebert",
      "orcid": "0000-0003-3329-3674"
    },
    {
      "affs": [
        11
      ],
      "name": "Nina Lin",
      "orcid": "0000-0002-4913-0442"
    },
    {
      "affs": [
        11
      ],
      "name": "Raffael Nachbagauer",
      "orcid": "0000-0001-5568-5420"
    },
    {
      "affs": [
        3,
        4,
        12,
        13,
        14
      ],
      "name": "Florian Krammer",
      "orcid": "0000-0003-4121-776X"
    },
    {
      "affs": [
        11
      ],
      "name": "Robert Paris",
      "orcid": "0000-0003-3234-5989"
    },
    {
      "affs": [
        15,
        16
      ],
      "name": "Jesse D. Bloom",
      "orcid": "0000-0003-1267-3408"
    },
    {
      "affs": [
        0
      ],
      "name": "Jackson S. Turner",
      "orcid": "0000-0002-4396-6265"
    },
    {
      "affs": [
        17,
        18,
        10,
        19
      ],
      "name": "Rachel M. Presti",
      "orcid": "0000-0002-5469-0727"
    },
    {
      "affs": [
        20,
        21,
        22
      ],
      "name": "Jiwon Lee",
      "orcid": "0000-0001-7835-3621"
    },
    {
      "affs": [
        23,
        24,
        25
      ],
      "name": "Ali H. Ellebedy",
      "orcid": "0000-0002-6129-2532"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/b549em4caqhgy.bib",
  "cited_by": 12,
  "doi": "10.1038/s41590-026-02569-5",
  "fulltext_url": null,
  "id": "b549em4caqhgy",
  "issns": [
    "1529-2908",
    "1529-2916"
  ],
  "landing_url": "https://doi.org/10.1038/s41590-026-02569-5",
  "language": "en",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
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      "2713|Influenza Virus Research Studies"
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  "openalex": "W7164830761",
  "pdf_url": "https://www.nature.com/articles/s41590-026-02569-5.pdf",
  "pmcid": "PMC11483064",
  "pmid": "39416092",
  "published": "2026-06-15",
  "publisher": "Nature Portfolio",
  "ris": "https://research.draconitic.com/paper/b549em4caqhgy.ris",
  "sources": [
    {
      "first_seen": "2026-11-04T13:21:15Z",
      "native_id": "W7164830761",
      "source": "openalex",
      "url": "https://doi.org/10.1038/s41590-026-02569-5"
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  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2713|Influenza Virus Research Studies",
      "subfield": "epidemiology-public-health"
    }
  ],
  "title": "mRNA-based influenza vaccine expands the B cell response breadth in humans",
  "title_text": "mRNA-based influenza vaccine expands the B cell response breadth in humans",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T13:21:16Z",
  "url": "https://research.draconitic.com/paper/b549em4caqhgy",
  "venue": "Nature Immunology",
  "versions": []
}