{
  "abstract": "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-gamma-associated myeloid inflammation upon secondary Delta infection. Using lymphoid-deficient mice that display female-biased resistance to Delta infection, IFN-gamma treatment provides partial protection to naive 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.",
  "abstract_shown": true,
  "affiliations": [
    "Boston University"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 14,
  "authors": [
    {
      "name": "D. Kenney"
    },
    {
      "name": "M. Matsuo"
    },
    {
      "name": "A. Pantelias"
    },
    {
      "name": "J. Leger"
    },
    {
      "name": "A. Kaplan"
    },
    {
      "name": "F. Cerbo"
    },
    {
      "name": "D.-Y. Chen"
    },
    {
      "name": "S. Adams"
    },
    {
      "name": "G. Unali"
    },
    {
      "name": "D. Wallace"
    },
    {
      "name": "M. Saeed"
    },
    {
      "name": "A. Belkina"
    },
    {
      "name": "C. Harly"
    },
    {
      "affs": [
        0
      ],
      "name": "F. Douam"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/c4hcf1a7yh48g.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.28.755090",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.28.755090v1.full",
  "id": "c4hcf1a7yh48g",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.28.755090v1",
  "language": null,
  "licence": "CC-BY-ND",
  "licence_label": "CC BY-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "immunology"
    ],
    [
      "openalex",
      "2725|SARS-CoV-2 and COVID-19 Research"
    ]
  ],
  "openalex": "W7219072044",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.28.755090v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-28",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/c4hcf1a7yh48g.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:25:55Z",
      "native_id": "10.64898/2026.09.28.755090",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.28.755090v2"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:immunology",
      "subfield": "immunology"
    }
  ],
  "title": "Male and female mice achieve equivalent protection against heterologous SARS-CoV-2 infection through divergent immune mechanisms",
  "title_text": "Male and female mice achieve equivalent protection against heterologous SARS-CoV-2 infection through divergent immune mechanisms",
  "type": "preprint",
  "updated_at": "2026-10-30T12:26:44Z",
  "url": "https://research.draconitic.com/paper/c4hcf1a7yh48g",
  "venue": "bioRxiv",
  "versions": []
}