BRIEF RESEARCH REPORT article
Front. Immunol.
Sec. Vaccines and Molecular Therapeutics
This article is part of the Research TopicCommunity Series in immune studies of SARS-CoV2 and vaccines using preclinical modeling, Volume IIView all 5 articles
Sex differences in vaccine-induced immunity in mice immunized with integrase-defective lentiviral vector delivering the SARS-CoV-2 Spike protein
Provisionally accepted
Iole Farina
Alessandra Gallinaro
Martina Borghi
Maria Franca PirilloChiara Falce
Andrea Canitano
Zuleika MicheliniAlice ZappitelliAntonio Di Virgilio
Mario Picozza
Andrea Cara*
Donatella Negri*- National Institute of Health (ISS), Rome, Italy
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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-Spike 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 strongly support the need of appropriate design of vaccine protocols both at the preclinical and clinical levels.
Keywords: Germinal Center, integrase defective lentiviral vector, neutralizing antibody, Preclinical study, sex differences, Spike, T cell response, Vaccine
Received: 30 Dec 2025; Accepted: 16 Feb 2026.
Copyright: © 2026 Farina, Gallinaro, Borghi, Pirillo, Falce, Canitano, Michelini, Zappitelli, Di Virgilio, Picozza, Cara and Negri. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Andrea Cara
Donatella Negri
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