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<p>Influenza viruses continue to cause a substantial global disease burden. Despite influenza vaccination, some individuals succumb to life-threatening influenza or death. Yet our understanding of immune features elicited by vaccination and influenza A and B virus&#xa0;(IAV, IBV) infection is limited. To define molecular signatures of influenza-specific B-cells, we performed scRNA-sequencing of influenza-specific B-cells in vaccinees and hospitalized IAV/IBV-infected patients using HA-probes. We observed increased interferon-stimulated gene signatures (<i>IF44L</i>, <i>IFITM1</i> and <i>XAF1</i>), in total B-cells from IBV-patients, but not at 1-month following patients’ recovery or in IAV-patients or vaccinees. Phenotypic differentiation and isotype class-switching of HA-specific B-cells were observed following vaccination, with clonal sharing between memory and atypical B-cell phenotypes. In-vitro influenza virus infection experiments showed IBVs having higher infectivity of human PBMCs, including B-cells, and reduced B-cell proliferation compared to IAV, potentially associated with antiproliferative effect of IFITM1. We provide key insights into B-cell immunity towards IBV and IAV infections and vaccination, which will inform rational vaccine design and therapeutic strategies aimed at eliciting robust HA-specific B-cell responses, while minimizing adverse effects caused by natural infection.</p>

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IFN-gene signatures in B cells following influenza A and B virus infection and influenza vaccination

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年3月9日

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  • Wuji Zhang,
  • E Kaitlynn Allen,
  • Shihan Li,
  • Ilariya Tarasova,
  • Rubaiyea Farrukee,
  • Lukasz Kedzierski,
  • Brad Gilbertson,
  • Hayley A McQuilten,
  • Jennifer R Habel,
  • Lilith F Allen,
  • Steven Rockman,
  • Sarah L Londrigan,
  • Stephen J Kent,
  • Adam K Wheatley,
  • Jason A Trubiano,
  • Tom C Kotsimbos,
  • Allen C Cheng,
  • Jan Schroeder,
  • Jeremy Chase Crawford,
  • Paul G Thomas,
  • Katherine Kedzierska,
  • Thi H O Nguyen

摘要

Influenza viruses continue to cause a substantial global disease burden. Despite influenza vaccination, some individuals succumb to life-threatening influenza or death. Yet our understanding of immune features elicited by vaccination and influenza A and B virus (IAV, IBV) infection is limited. To define molecular signatures of influenza-specific B-cells, we performed scRNA-sequencing of influenza-specific B-cells in vaccinees and hospitalized IAV/IBV-infected patients using HA-probes. We observed increased interferon-stimulated gene signatures (IF44L, IFITM1 and XAF1), in total B-cells from IBV-patients, but not at 1-month following patients’ recovery or in IAV-patients or vaccinees. Phenotypic differentiation and isotype class-switching of HA-specific B-cells were observed following vaccination, with clonal sharing between memory and atypical B-cell phenotypes. In-vitro influenza virus infection experiments showed IBVs having higher infectivity of human PBMCs, including B-cells, and reduced B-cell proliferation compared to IAV, potentially associated with antiproliferative effect of IFITM1. We provide key insights into B-cell immunity towards IBV and IAV infections and vaccination, which will inform rational vaccine design and therapeutic strategies aimed at eliciting robust HA-specific B-cell responses, while minimizing adverse effects caused by natural infection.