HYDROGEN PEROXIDE GENERATING LACTOBACILLI AND MONOPEROXIDASE AS MICROBICIDES

过氧化物酶、过氧化氢和卤化物形成了一个强大的抗菌系统 对多种微生物有效。过氧化物酶存在于 阴道液某些但不是全部女性的阴道液或宫颈粘液一个 阴道中过氧化氢的主要来源是乳酸菌，包括 乳酸菌。然而，只有一半的性活跃女性参加了 横断面研究表明，阴道中有产生过氧化氢的乳酸菌。 已公布的数据表明，仅产生过氧化氢的乳酸菌 在高浓度下对HLV-1有致病作用，在过氧化氢水平下 单独生产乳酸菌是无效的，添加过氧化物酶 卤化物(Cl-)恢复了杀灭病毒的活性。这样做的长期目标是 研究目的是评估一种含有过氧化物酶的栓剂的效果。 再加上生殖器感染时产生过氧化氢的乳酸菌。 在这项拟议的研究中，乳酸菌的特性- 将在阴道中评估过氧化物酶-卤化物抗菌系统 感染和未感染HLV的妇女。一种复方栓剂 含产H_2O_2乳酸菌和重组 将开发髓过氧化物酶并在体外测试其保留 其杀菌和杀病毒(HLV-1)效果。这种组合 栓剂将在非人类灵长类动物体内进行检查，以评估其 对阴道菌群和上皮细胞的影响。浅谈栓剂的作用 关于宫颈沙眼衣原体和HLV-2在猴体内的感染 已评估。如果在猴子模型中观察到适当的低毒性， 联合栓剂将用于HLV感染和未感染患者 妇女评估这种内源性杀菌剂的补充是否 降低了在女性脱毒患者中检测HLV的能力。这个 复方栓剂对阴道菌群及上皮细胞的影响 将对HLV阳性和阴性妇女进行评估。 这一系列的研究-将使我们更好地理解 内源性杀菌系统在维持正常 阴道生态系统，并将决定是否补充 外源乳酸菌和过氧化物酶可减少某些病毒的传播 性传播疾病。 该项目将涉及通过临床招募的人类受试者 核心。该栓剂将在灵长类动物身上进行评估(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菌系统。这 信息与阴道杀菌剂的方方面面有关 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.