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<p>Antibodies are central to immune defenses. Despite advances in understanding the mechanisms of antibody generation, a comprehensive model of how intrinsic and external factors shape human humoral responses to viruses has been lacking. Here we apply phage immunoprecipitation sequencing to investigate the effects of demographic factors—including 108 lifestyle and health-related variables—and genetic variation on antibody reactivity to over 97,000 viral peptides in 1,212 healthy adults. We demonstrate that age, sex and continent of birth extensively affect not only the viruses but also the specific viral epitopes targeted by the antibody repertoire. Notably, we find that antibodies against rapidly evolving epitopes of influenza A virus decrease with age, whereas immunoreactivity to conserved epitopes increases. Furthermore, we identify strong associations between antibodies against 34 viruses and genetic variants at <i>HLA</i>, <i>FUT2</i>, <i>IGH</i> and <i>IGK</i> loci, some of which increase autoimmune disease risk. These findings offer a valuable resource for understanding the factors affecting antibody-mediated immunity, laying the groundwork for optimizing vaccine strategies.</p>

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Demographic and genetic factors shape the epitope specificity of the human antibody repertoire against viruses

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年2月16日

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  • Axel Olin,
  • Christian Pou,
  • Anthony Jaquaniello,
  • Jack Crook,
  • Ziyang Tan,
  • Maguelonne Roux,
  • Florian Dubois,
  • Bruno Charbit,
  • Dang Liu,
  • Françoise Donnadieu,
  • Laura Garcia,
  • Camille Lambert,
  • Emma Bloch,
  • Emmanuel Clave,
  • Itauá Leston Araujo,
  • Antoine Toubert,
  • Maxime Rotival,
  • Etienne Simon-Lorière,
  • Michael White,
  • Petter Brodin,
  • Darragh Duffy,
  • Lluis Quintana-Murci,
  • Etienne Patin,
  • Laurent Abel,
  • Andres Alcover,
  • Hugues Aschard,
  • Philippe Bousso,
  • Nollaig Bourke,
  • Pierre Bruhns,
  • Nadine Cerf-Bensussan,
  • Ana Cumano,
  • Christophe D’Enfert,
  • Caroline Demangel,
  • Ludovic Deriano,
  • Marie-Agnès Dillies,
  • James Di Santo,
  • Gérard Eberl,
  • Jost Enninga,
  • Jacques Fellay,
  • Ivo Gomperts-Boneca,
  • Milena Hasan,
  • Gunilla Karlsson Hedestam,
  • Serge Hercberg,
  • Molly A. Ingersoll,
  • Olivier Lantz,
  • Rose Anne Kenny,
  • Mickaël Ménager,
  • Frédérique Michel,
  • Hugo Mouquet,
  • Cliona O’Farrelly,
  • Antonio Rausell,
  • Frédéric Rieux-Laucat,
  • Lars Rogge,
  • Magnus Fontes,
  • Anavaj Sakuntabhai,
  • Olivier Schwartz,
  • Benno Schwikowski,
  • Spencer Shorte,
  • Frédéric Tangy,
  • Mathilde Touvier,
  • Marie-Noëlle Ungeheuer,
  • Christophe Zimmer,
  • Matthew L. Albert

摘要

Antibodies are central to immune defenses. Despite advances in understanding the mechanisms of antibody generation, a comprehensive model of how intrinsic and external factors shape human humoral responses to viruses has been lacking. Here we apply phage immunoprecipitation sequencing to investigate the effects of demographic factors—including 108 lifestyle and health-related variables—and genetic variation on antibody reactivity to over 97,000 viral peptides in 1,212 healthy adults. We demonstrate that age, sex and continent of birth extensively affect not only the viruses but also the specific viral epitopes targeted by the antibody repertoire. Notably, we find that antibodies against rapidly evolving epitopes of influenza A virus decrease with age, whereas immunoreactivity to conserved epitopes increases. Furthermore, we identify strong associations between antibodies against 34 viruses and genetic variants at HLA, FUT2, IGH and IGK loci, some of which increase autoimmune disease risk. These findings offer a valuable resource for understanding the factors affecting antibody-mediated immunity, laying the groundwork for optimizing vaccine strategies.