Increased HIV susceptibility has been associated with the progesterone-dominant luteal phase of the menstrual cycle and the use of progesterone-only contraceptives, yet the mechanism is poorly understood. Here, we performed mass spectrometry-based analyses of cervicovaginal fluids collected from women with differing ovarian hormone levels as demonstrated by menstrual cycle phase or exogenous progesterone-only contraceptive use. We found that proteins associated with maintaining the integrity of epithelial barrier were enriched during times of high estradiol, whereas during times of high progesterone, there was a loss of barrier integrity proteins and an enrichment of proteins with known roles in inflammatory processes including leukocyte infiltration. Progesterone-based proteomic profiles were also strongly associated with neutrophil signatures with some evidence of CD4+ T cell signatures. This study generates new hypotheses about the potential mechanisms of hormone-associated HIV susceptibility including a weakened epithelial barrier and increased HIV target cell recruitment during times of increased progesterone. / February 2016

A human safe, Alhydrogel adjuvanted whole cell Trichomonas vaginalis vaccine was tested for efficacy in a BALB/c mouse model of vaginal infection. Additionally, the systemic and local immune response were measured. Vaccination reduced incidence and increased clearance of infection, and induced both systemic and local humoral immune responses. CD4+ cells were detected in vaginal tissues following intravaginal challenge with T. vaginalis, but were not seen in uninfected mice. CD4+ cells were detected more often, earlier, and in greater numbers in vaccinated vaginal tissues compared to unvaccinated controls. Presence of CD4+ T cells following infection can have significant implications of increasing HIV susceptibility and transmission. These data suggest that the vaccine induces local and systemic immune responses, and confers significantly greater protection against vaginal challenge than unvaccinated vaginal challenge. These data support the potential for a human vaccine against T. vaginalis infection that could also impact the incidence of HIV infections.

A human safe, Alhydrogel adjuvanted whole cell Trichomonas vaginalis vaccine was tested for efficacy in a BALB/c mouse model of vaginal infection. Additionally, the systemic and local immune response were measured. Vaccination reduced incidence and increased clearance of infection, and induced both systemic and local humoral immune responses. CD4+ cells were detected in vaginal tissues following intravaginal challenge with T. vaginalis, but were not seen in uninfected mice. CD4+ cells were detected more often, earlier, and in greater numbers in vaccinated vaginal tissues compared to unvaccinated controls. Presence of CD4+ T cells following infection can have significant implications of increasing HIV susceptibility and transmission. These data suggest that the vaccine induces local and systemic immune responses, and confers significantly greater protection against vaginal challenge than unvaccinated vaginal challenge. These data support the potential for a human vaccine against T. vaginalis infection that could also impact the incidence of HIV infections.