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

New publication for HKU-Pasteur’s Wuji Zhang! Published in EMBO Molecular Medicine, the study explores how the human immune system responds to influenza vaccination and natural infection by dissecting the molecular features of influenza‑specific B cells. Using single‑cell RNA sequencing, the team compared responses to influenza A and B viruses and uncovered striking differences—particularly a strong interferon‑driven signature in B cells from influenza B patients. Their findings reveal how vaccination shapes B‑cell differentiation and how influenza B viruses may directly impair B‑cell function, offering valuable insights for designing more effective and safer influenza vaccines.

Abstract: 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.

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