HYDROGEN PEROXIDE GENERATING LACTOBACILLI AND MONOPEROXIDASE AS MICROBICIDES

过氧化物酶，H2O2和卤化物形成一个强大的抗菌系统

Peroxidase, H2O2 and a halide form a powerful antimicrobial system effective against a variety of microorganisms. Peroxidase is present in the vaginal fluid or cervical mucous of some, but not all, women. A primary source of H2O2 in the vagina is lactic acid bacteria including lactobacilli. However, only half of sexually active women enrolled in cross-sectional studies have H2O2 producing lactobacilli in the vagina. Published data has demonstrated that H2O2-producing lactobacilli alone at high concentrations are viricidal to HlV-1 and at levels where H2O2 producing lactobacilli are ineffective alone, the addition of peroxidase and halide (Cl-) restored viricidal activity. The long term goals of this study are to assess the effect of a suppository containing peroxidase plus H2O2-producing lactobacilli on genital infections. In this proposed study, the characteristics of the lactobacillus- peroxidase-halide anti-microbial system will be evaluated in the vagina of HlV-infectent and noninfected women. A combination suppository containing both H2O2-generating lactobacilli and recombinant myeloperoxidase will be developed and tested in vitro for retention of its bactericidal and viricidal (HlV-1) effectiveness. This combination suppository will be examined in vivo in nonhuman primates to assess its effect on the vaginal flora and epithelium. The effect of the suppository on cervical C. trachomatis and HlV-2 infection in the monkey will be evaluated. If suitably low toxicity is observed in the monkey model, the combination suppository will be applied in HlV-infected and uninfected women to assess whether supplementation of this endogenous microbicide decreases the ability to detect HlV among women shedding virus. The effect of the combination suppository on the vaginal flora and epithelium of HlV-positive and negative women will be evaluated. This series of studies-will lead to a greater understanding of the role of the endogenous microbicidal system in the maintenance of a normal vaginal ecosystem, and will determine whether supplementation with exogenous lactobacilli and peroxidase could decrease transmission of some STDs. This project will involve human subjects recruited through the clinical core. The suppository will be evaluated in both primates (project 1) and humans (core D). This project will contribute to the overall program by better defining the endogenous microbicidal systems in the vagina. This information has relevance to all aspects of vaginal microbicide development.