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Despite high incidence rates, increasing drug resistance, and potential teratogenic effects of current treatments, there are no approved fungal vaccines. Previously, we generated a recombinant \u2018pan-fungal\u2019 vaccine candidate, NXT-2, which demonstrated protection against multiple fungal infections including invasive candidiasis. Here, we evaluated the protective efficacy of NXT-2 against <jats:italic>Candida albicans<\/jats:italic> in a murine VVC model. NXT-2 was highly immunogenic, eliciting localized immune responses in the vaginal mucosa. NXT-2 immunized mice had reduced fungal burden and polymorphonuclear neutrophil (PMN) recruitment into the vaginal lumen following <jats:italic>C. albicans<\/jats:italic> challenge compared to sham immunized mice. PMNs in the vaginal lumen of NXT-2 immunized mice were associated with <jats:italic>C. albicans<\/jats:italic> hyphae, which was absent in controls. NXT-2 immunization reduces vaginal tissue damage and inflammation, while providing antibody-mediated protection, demonstrating the potential of the vaccine for the prevention of VVC.<\/jats:p>","DOI":"10.1038\/s41541-025-01171-4","type":"journal-article","created":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T17:32:07Z","timestamp":1748885527000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Protective efficacy of the pan-fungal vaccine NXT-2 against vulvovaginal candidiasis in a murine model"],"prefix":"10.1038","volume":"10","author":[{"given":"Daniel A.","family":"Wychrij","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taylor I.","family":"Chapman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Rayens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Whitney","family":"Rabacal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hubertine M. 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An approved plan is in place with the University of Georgia for managing potential conflicts. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"112"}}