Evaluate test formulations of microbicide combinations being developed in Subprojects 0001 and 0002 for protective efficacy in the mouse/HSV vaginal challange model, toxic effects in the post-exposure HSV susceptiblity model and the inflammatory cell entry model, effects in vitro on vaginal flora and pathogens, and contraceptive efficacy in the rabbit.
Specific Aims : 1) Protective efficacy, and duration of protection, for blocking vaginal transmission of HSV-2 infections will be evaluated in progestin-treated mice. 2) Toxic effects on columnar epithelium will be evaluated in progestin-treated mice12 hours after a single vaginal application of the test formulation by determining whether susceptibility to a low dose of HSV-2 is increased, and by observing whether vaginal entry of inflammatory cells (macrophages) is increased. 3) Effects of test formulations will be evaluated in vitro on 4 strains of human vaginal lactobacilli (L. jensenii, L. crispatus, L. vaginalis, L. gasseri) to determine minimum inhibitory concentration (MIC50). If non-toxic to lactobacilli, they will be tested in vitro against BV-associated organisms (G. vaginalis, M. hominis, P. bivia), vaginal pathogens (S. aureus, C. albicans, E. coli) and STD pathogens (N. gonorrhea, T. vaginalis). 4) Retention, vaginal distribution, and sub-epithelial penetration of fluorescently labeled dendrimers will be investigated in the progestin-treated mouse to help optimize gel formulations & dendrimer characteristics. 5) Contraceptive efficacy, and duration of protection, will be evaluated in the rabbit using artificial insemination.
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