ArticleFrontiers in immunology2026
Sex differences in vaccine-induced immunity in mice immunized with integrase-defective lentiviral vector delivering the SARS-CoV-2 Spike protein.
Article in Frontiers in immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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Authors and funding
12 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Introduction: Integrase-defective lentiviral vector (IDLV) delivering the optimized SARS-CoV-2 Spike protein induces strong and persistent immunity in mice. Here, we investigate potential sex-dependent differences by comparing female and male mice for germinal center (GC) reactions and Spike-specific immune responses induced by IDLV delivering an optimized SARS-CoV-2 Spike Wuhan-Hu-1 protein (IDLV-S). Methods: Female and male BALB/c mice were injected once intramuscularly with either IDLV-S or IDLV-Mock or were left untreated. Blood, lymph nodes and spleens were collected at selected time points for the analysis of immune responses by flow cytometry, FluoroSpot and neutralization assays. Results: Strong GC activation was detected at 7 days from the immunization in all vaccinated mice, showing a higher percentage of GC B cells in females. Anti-Spike neutralizing antibodies (nAbs) and T cell responses were detected up to 24 weeks from immunization in all IDLV-S immunized mice. NAbs in sera were more persistent in female than in male mice, and vaccinated females also showed a higher cross-neutralization activity against Spikes from variants of concern, reflecting a better quality of the functional immune response. Both IDLV-S immunized groups showed specific T cell responses evaluated as IFNγ/TNFα producing T cells, with a higher response in females. Discussion: The higher GC reaction in the immunized females can be the trigger for the more persistent and broader nAb response in females compared to males. Our data confirm sex-dependent vaccine-induced immune responses and support the need of appropriate design of vaccine protocols both at the preclinical and clinical levels.
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