{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T13:51:36Z","timestamp":1772632296792,"version":"3.50.1"},"reference-count":64,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T00:00:00Z","timestamp":1772582400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>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).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>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 IFN\u03b3\/TNF\u03b1 producing T cells, with a higher response in females.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1778067","type":"journal-article","created":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T06:58:51Z","timestamp":1772607531000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Sex differences in vaccine-induced immunity in mice immunized with integrase-defective lentiviral vector delivering the SARS-CoV-2 Spike protein"],"prefix":"10.3389","volume":"17","author":[{"given":"Iole","family":"Farina","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases, Istituto Superiore di Sanit\u00e0","place":["Rome, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandra","family":"Gallinaro","sequence":"additional","affiliation":[{"name":"National Center for Global Health, Istituto Superiore di Sanit\u00e0","place":["Rome, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martina","family":"Borghi","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Istituto Superiore di Sanit\u00e0","place":["Rome, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Franca","family":"Pirillo","sequence":"additional","affiliation":[{"name":"National Center for Global Health, Istituto Superiore di Sanit\u00e0","place":["Rome, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiara","family":"Falce","sequence":"additional","affiliation":[{"name":"National Center for Global Health, Istituto Superiore di Sanit\u00e0","place":["Rome, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Canitano","sequence":"additional","affiliation":[{"name":"National Center for Global Health, Istituto Superiore di Sanit\u00e0","place":["Rome, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zuleika","family":"Michelini","sequence":"additional","affiliation":[{"name":"National Center for Global Health, Istituto Superiore di Sanit\u00e0","place":["Rome, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alice","family":"Zappitelli","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Istituto Superiore di Sanit\u00e0","place":["Rome, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"Di Virgilio","sequence":"additional","affiliation":[{"name":"Center for Animal Research and Welfare, Istituto Superiore di Sanit\u00e0","place":["Rome, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mario","family":"Picozza","sequence":"additional","affiliation":[{"name":"Core Facilities, Cytometry Area, Istituto Superiore di Sanit\u00e0","place":["Rome, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Cara","sequence":"additional","affiliation":[{"name":"National Center for Global Health, Istituto Superiore di Sanit\u00e0","place":["Rome, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donatella","family":"Negri","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Istituto Superiore di Sanit\u00e0","place":["Rome, Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1038\/s41577-024-00996-9","article-title":"The conneXion between sex and immune responses","volume":"24","author":"Forsyth","year":"2024","journal-title":"Nat Rev Immunol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26157101","article-title":"Understanding sex differences in autoimmune diseases: immunologic mechanisms","volume":"26","author":"Kim","year":"2025","journal-title":"Int J.Mol. 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