{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:19:32Z","timestamp":1792790372014,"version":"4.5.0"},"posted":{"date-parts":[[2026,10,3]]},"group-title":"Immunology","reference-count":50,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T00:00:00Z","timestamp":1790985600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nd\/4.0\/"}],"funder":[{"name":"Boston University\/NEIDL","id":[{"id":"https:\/\/ror.org\/05qwgg493","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Hartwell Foundation","award":["55212221"],"award-info":[{"award-number":["55212221"]}],"id":[{"id":"https:\/\/ror.org\/038cgyc59","id-type":"ROR","asserted-by":"crossref"}]},{"name":"NIH","award":["UL1 TR001430"],"award-info":[{"award-number":["UL1 TR001430"]}]},{"name":"NIH","award":["T32AI007309"],"award-info":[{"award-number":["T32AI007309"]}]},{"name":"NIH","award":["AG078814"],"award-info":[{"award-number":["AG078814"]}]},{"name":"NIH","award":["CA259635"],"award-info":[{"award-number":["CA259635"]}]},{"name":"DOW","award":["W81XMH2110128 PR202887"],"award-info":[{"award-number":["W81XMH2110128 PR202887"]}]},{"name":"Boston University ARC-COVID19","id":[{"id":"https:\/\/ror.org\/05qwgg493","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,10,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>Biological sex is a major determinant of antiviral immunity, yet how it shapes lung-resident antiviral immunity remains poorly understood. We report that prior mild SARS-CoV-2 BA.1 infection protects mice from lethal heterologous Delta challenge through distinct sex-biased immune mechanisms. Although heterologous protection is clinically equivalent between sexes, T- and B-cell depletions before BA.1 exposure abrogate protection only in males. Depletion with anti-CD4, but not anti-CD8, abolishes protection in both sexes, but co-depletion with anti-CD4\/anti-CD8 partially restores protection in females only. Further, females exhibit enhanced IFN\u03b3-associated myeloid inflammation upon secondary Delta infection. Using lymphoid-deficient mice that display female-biased resistance to Delta infection, IFN\u03b3 treatment provides partial protection to na\u00efve males against Delta. Female resistance is lost after previous BA.1 exposure, highlighting the importance of lymphoid-mediated inflammatory regulation. Together, equivalent antiviral protection against heterologous respiratory viral infection is governed by sexually dimorphic mechanisms, with significant implications for designing mucosal vaccines and immunotherapies.<\/jats:p>","DOI":"10.64898\/2026.09.28.755090","type":"posted-content","created":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T04:40:15Z","timestamp":1791088815000},"source":"Crossref","is-referenced-by-count":0,"title":["Male and female mice achieve equivalent protection against heterologous SARS-CoV-2 infection through divergent immune mechanisms"],"prefix":"10.64898","author":[{"given":"Devin","family":"Kenney","sequence":"first","affiliation":[{"name":"Department of Virology, Immunology, and Microbiology, Boston University Chobanian and Avedisian School of Medicine, Boston, MA, USA"},{"name":"Department of Biochemistry and Cell Biology, Boston University Chobanian and Avedisian School of Medicine, Boston MA, USA"},{"name":"National Emerging Infectious Diseases 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Biology, Boston University Chobanian and Avedisian School of Medicine, Boston MA, USA"},{"name":"National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott R.","family":"Adams","sequence":"additional","affiliation":[{"name":"Department of Virology, Immunology, and Microbiology, Boston University Chobanian and Avedisian School of Medicine, Boston, MA, USA"},{"name":"National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Unali","sequence":"additional","affiliation":[{"name":"Department of Virology, Immunology, and Microbiology, Boston University Chobanian and Avedisian School of Medicine, Boston, MA, USA"},{"name":"National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas 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