Protective efficacy of the pan-fungal vaccine NXT-2 against vulvovaginal candidiasis in a murine model
Daniel A. Wychrij, Taylor I. Chapman, Emily Rayens, Whitney Rabacal, Hubertine M. E. Willems, Kwadwo O. Oworae, Brian M. Peters, Karen A. Norris
Abstract
Vulvovaginal candidiasis (VVC) is the most common clinical manifestation of candidiasis, affecting 75% of women. 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 'pan-fungal' vaccine candidate, NXT-2, which demonstrated protection against multiple fungal infections including invasive candidiasis. Here, we evaluated the protective efficacy of NXT-2 against Candida albicans 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 C. albicans challenge compared to sham immunized mice. PMNs in the vaginal lumen of NXT-2 immunized mice were associated with C. albicans 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.