tetano
Editor, Senior Moderator
Front Immunol
. 2026 Mar 4:17:1778067.
doi: 10.3389/fimmu.2026.1778067. eCollection 2026.
Sex differences in vaccine-induced immunity in mice immunized with integrase-defective lentiviral vector delivering the SARS-CoV-2 Spike protein
Iole Farina[SUP] #[/SUP][SUP] 1 [/SUP], Alessandra Gallinaro[SUP] #[/SUP][SUP] 2 [/SUP], Martina Borghi[SUP] 1 [/SUP], Maria Franca Pirillo[SUP] 2 [/SUP], Chiara Falce[SUP] 2 [/SUP], Andrea Canitano[SUP] 2 [/SUP], Zuleika Michelini[SUP] 2 [/SUP], Alice Zappitelli[SUP] 1 [/SUP], Antonio Di Virgilio[SUP] 3 [/SUP], Mario Picozza[SUP] 4 [/SUP], Andrea Cara[SUP] 2 [/SUP], Donatella Negri[SUP] 1 [/SUP]
Affiliations
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.
Keywords: Spike; T cell response; germinal center; integrase-defective lentiviral vector; neutralizing antibody; preclinical study; sex differences; vaccine.
. 2026 Mar 4:17:1778067.
doi: 10.3389/fimmu.2026.1778067. eCollection 2026.
Sex differences in vaccine-induced immunity in mice immunized with integrase-defective lentiviral vector delivering the SARS-CoV-2 Spike protein
Iole Farina[SUP] #[/SUP][SUP] 1 [/SUP], Alessandra Gallinaro[SUP] #[/SUP][SUP] 2 [/SUP], Martina Borghi[SUP] 1 [/SUP], Maria Franca Pirillo[SUP] 2 [/SUP], Chiara Falce[SUP] 2 [/SUP], Andrea Canitano[SUP] 2 [/SUP], Zuleika Michelini[SUP] 2 [/SUP], Alice Zappitelli[SUP] 1 [/SUP], Antonio Di Virgilio[SUP] 3 [/SUP], Mario Picozza[SUP] 4 [/SUP], Andrea Cara[SUP] 2 [/SUP], Donatella Negri[SUP] 1 [/SUP]
Affiliations
- PMID: 41859099
- PMCID: PMC12996097
- DOI: 10.3389/fimmu.2026.1778067
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.
Keywords: Spike; T cell response; germinal center; integrase-defective lentiviral vector; neutralizing antibody; preclinical study; sex differences; vaccine.