ZCM:A NOVEL BROAD-SPECTRUM MICROBICIDE FOR SEXUALLY TRANSMITTED INFECTIONS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 根据3219协议，我们在PC-815(CarraGuard+MIV-150的50微摩尔)上推进了我们的研究，我们正在探索PC-1005(CarraGuard+MIV-150的50微摩尔和0.3%锌)的杀菌活性。动物每天涂抹凝胶2周，然后在最后一次凝胶4-8小时后经阴道激发SHV RT。最初，当动物在最后一次凝胶后4小时受到攻击时，我们观察到100%的保护作用，随后的研究证实，这种保护能力持续到8小时(每组感染0/7，而安慰剂组为9/10)。这表明PC-1005在预防感染方面比PC-815(2/6感染)或CarraGuard(4/6感染)更有效。接下来的研究将测试PC-1005在最后一次凝胶应用后是否仍有效长达24小时。我们还计划包括PC-707(CarraGuard加0.3%锌)的额外对照，以确定PC-1005活性增加是由于MIV-150与锌结合还是单独使用锌造成的。这些动物将在3月份接受挑战，这些关于PC-1005的初步研究预计将在今年年底完成。PK研究计划与这些最终疗效研究并行进行。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Advancing our studies on PC-815 (Carraguard plus 50-micromolar of MIV-150) under protocol 3219, we are exploring the microbicide activity of PC-1005 (Carraguard plus 50-micromolar of MIV-150 and 0.3% zinc). Animals received daily applications of gel for 2 weeks and were then vaginally challenged with SHIV RT 4-8h after the last gel. Initially, we observed 100% protection when the animals were challenged 4h after the last gel and subsequent studies have confirmed that this protective capacity persisted for up to 8h (0/7 infected in each group compared to 9/10 in the placebo group). This demonstrates that PC-1005 is more effective at preventing infection that PC-815 (2/6 infected) or Carraguard (4/6 infected). The next studies will test whether PC-1005 remains effective for up to 24h post the last gel application. We also plan to include the additional control of PC-707 (Carraguard plus 0.3% zinc) to determine if the increased activity of PC-1005 is due to the combination of MIV-150 and zinc or zinc alone. The animals will get challenged in March and these initial studies on PC-1005 are expected to be completed by the end of the year. PK studies are planned to be run in parallel to these final efficacy studies.