HYDROGEN PEROXIDE GENERATING LACTOBACILLI AND MONOPEROXIDASE AS MICROBICIDES

过氧化物酶、H2 O2和卤化物形成强大的抗微生物系统 对多种微生物有效。过氧化物酶存在于 阴道分泌物或子宫颈粘液的一些，但不是全部，妇女。一 阴道中H2 O2的主要来源是乳酸菌， 乳酸杆菌。然而，只有一半的性活跃妇女参加了 横断面研究表明阴道中存在产生H2 O2的乳酸杆菌。 已发表的数据表明，单独产生H2 O2的乳酸杆菌 在高浓度下对HIV-1有杀病毒作用， 单独生产乳酸杆菌是无效的，添加过氧化物酶 卤化物（Cl-）恢复杀病毒活性。这一长期目标 研究是评估含有过氧化物酶的栓剂的作用 再加上能产生H2 O2的乳酸杆菌来治疗生殖器感染 在这项研究中，研究人员发现， 将在阴道中评价过氧化物酶-卤化物抗微生物系统 HIV感染者和未感染者的对比一种复方栓剂 含有产生H2 O2的乳酸杆菌和重组 髓过氧化物酶将在体外开发和测试，以保留 其杀菌和杀病毒（HIV-1）的有效性。这种组合 栓剂将在非人灵长类动物体内进行检查， 对阴道植物群和上皮的影响。栓剂的作用 在颈C沙眼和HlV-2感染的猴子 评估。如果在猴模型中观察到适当低的毒性， 联合栓剂将用于HIV感染和未感染 妇女评估是否补充这种内源性杀微生物剂 降低了在妇女中检测HIV的能力。的 复方栓剂对阴道植物群和上皮的影响 HIV阳性和阴性的女性将被评估。 这一系列的研究-将导致更大的了解的作用 内源性杀微生物系统在维持正常的 阴道生态系统，并将确定是否补充 外源性乳酸杆菌和过氧化物酶可减少某些 性病 该项目将涉及通过临床招募的人类受试者， 核心将在灵长类动物（项目1）和 人类（核心D）。该项目将通过以下方式为整个计划做出贡献： 更好地定义阴道内的内源性杀微生物系统。这 信息与阴道杀微生物剂的所有方面都相关 发展

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.