IFN-gene signatures in B cells following influenza A and B virus infection and influenza vaccination
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.
Authors
- Paul Glyndwr Thomas (ORCID: https://orcid.org/0000-0001-7955-0256)
- Jennifer R. Habel (ORCID: https://orcid.org/0000-0003-0380-1527)
- Steven Rockman
- Ilariya Tarasova (ORCID: https://orcid.org/0000-0002-0895-9385)
- S.B.H. Kent
- Allen Cheng
- Rubaiyea Farrukee (ORCID: https://orcid.org/0000-0001-9023-246X)
- Jason A. Trubiano (ORCID: https://orcid.org/0000-0002-5111-6367)
- Hayley A. McQuilten (ORCID: https://orcid.org/0000-0002-7089-5300)
- Sarah L. Londrigan (ORCID: https://orcid.org/0000-0003-0989-4971)
- Wuji Zhang (ORCID: https://orcid.org/0000-0001-7460-4956)
- Brad Gilbertson (ORCID: https://orcid.org/0000-0001-7921-0032)
- Jan Schroeder (ORCID: https://orcid.org/0000-0001-5270-0605)
- Shihan Li (ORCID: https://orcid.org/0000-0003-3207-7064)
- Lukasz Kedzierski
- Tom Kotsimbos
- LJ Allen
- Jeremy Chase Crawford
- E Kaitlynn Allen
- Katherine Kedzierska
- Adam K Wheatley
- Thi H O Nguyen
Institutions
- CSL (United Kingdom) (GB)
- St. Jude Children's Research Hospital (US)
- Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa (ZA)
- Infectious Disease Research Institute (US)
- The University of Melbourne (AU)
- Walter and Eliza Hall Institute of Medical Research (AU)
- Peter MacCallum Cancer Centre (AU)
- The Alfred Hospital (AU)
- Monash Alfred Psychiatry Research centre (AU)
- Peter Doherty Institute (AU)
- Monash Health (AU)
- HKU-Pasteur Research Pole (HK)
- Austin Health (AU)
- Monash University (AU)
- University of Hong Kong (HK)
Publication Details
- Journal
- EMBO Molecular Medicine
- Published
- 2026-03-09
- DOI
- https://doi.org/10.1038/s44321-026-00395-8
- Citations
- 1
- Primary Topic
- Influenza Virus Research Studies
- Type
- article
- Field-Weighted Citation Impact
- 31.52
Funders
- National Institutes of Health
- Medical Research Council
- National Health and Medical Research Council
- National Institute of Allergy and Infectious Diseases