Project Grant R21AI185365

Award Date 6/21/24
Completion Date 4/30/26
Dollars Obligated $883K
Federal Grant Program
93.855
Assistance Type
Project Grant
Place of Performance
Pittsburgh, PA 15222, USA
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MUCOSAL HOST DEFENSE AGAINST VAGINAL CANDIDIASIS - ABSTRACT VULVOVAGINAL CANDIDIASIS (VVC) IS A WIDESPREAD MUCOSAL INFECTION CAUSED PREDOMINANTLY BY THE COMMENSAL FUNGUS CANDIDA ALBICANS. VVC IS A GLOBAL HEALTH CONCERN DUE TO ITS HIGH PREVALENCE IN IMMUNOCOMPETENT WOMEN (>75% INCIDENCE). ALTHOUGH NOT FATAL, APPROXIMATELY 15% OF WOMEN EXPERIENCE VVC RECURRENTLY, RESULTING IN SERIOUS IMPACTS ON QUALITY OF LIFE AND SIGNIFICANT COST BURDEN. THERE ARE NO LICENSED VACCINES TO ANY FUNGAL PATHOGENS. WHILE MUCH HAS BEEN LEARNED ABOUT IMMUNITY TO C. ALBICANS IN OTHER SITES (MOUTH, GUT, SKIN), OUR UNDERSTANDING OF IMMUNITY AT THE VAGINAL MUCOSA IS COMPARATIVELY LIMITED. CONTROL OF C. ALBICANS IN MOUTH AND SKIN UNQUESTIONABLY REQUIRES TH17 CELLS/IL-17, BUT THE ROLE OF THE TH17 PATHWAY IN VVC IS CONTROVERSIAL. WOMEN WITH HIV/AIDS OR RARE TH17/IL-17 RECEPTOR GENETIC DEFICIENCIES ARE NOT THOUGHT TO HAVE ABNORMAL INCIDENCES OF VVC, YET TH17 SIGNATURES ARE UPREGULATED IN VVC, AND VVC IS A STATISTICALLY SIGNIFICANT ADVERSE EVENT ASSOCIATED WITH IL-17 OR OTHER ANTI-CYTOKINE BLOCKADE. HERE WE SHOW THAT MULTIPLE CYTOKINES IN THE TH17 AXIS ACT IN CONCERT TO PROMOTE IMMUNITY TO VVC, AND WE WILL PROBE THE ESSENTIAL CORRELATES THAT DRIVE IMMUNITY IN THIS MUCOSAL SETTING FROM BOTH THE HOST AND THE FUNGAL SIDE.

Posted 6/21/24, 12:00 AM