BLOCKING VIRUS SPREAD BY DCS WITH CARRAGEENAN-BASED COMPOUNDS

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。 为了完成我们的测试，证明PC-817(CarraGuard+500微摩尔MIV-150 vs CarraGuard和安慰剂羟甲基纤维素，HMC)在预防猕猴阴道SHV-RT感染方面有效，我们最近挑战了最后几组动物(为103 TCID50挑战，每个主要测试组提供7只动物，以获得更强大的数据集)。使用回收的动物(早期挑战中未感染的动物)，我们还测试了MIV-150单独(在HMC中)的抗病毒效果，作为NNRTI在阴道应用时可以起作用的概念的证据。在104次TCID50攻击前30分钟，在HMC中单次注射500微摩尔的MIV-150对感染(2/2感染)的影响很小。然而，在104 TCID50病毒挑战的前一天、第二天和第二天应用凝胶可以减少感染。7只动物中3只感染典型的病毒血症，1只未感染，3只低水平感染，最高病毒载量为2100拷贝/毫升(随时间推移无法检测到)。这些动物的抗CD8治疗(大约5个月后)没有显示出“受控”感染(血浆中没有病毒尖峰)，这表明低水平的感染已经被清除。测试较低的103 TCID50疫苗，我们确认在103 TCID50挑战前30分钟在HMC中接种MIV-150后，3只动物中有2只保持未感染状态。在用103TCID50的Shiv-RT挑战之前30分钟，在HMC中接受500微摩尔MIV-150的其他动物只是被挑战来完成与CarraGuard和PC-817处理的动物的比较。

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. To complete our tests demonstrating that PC-817 (Carraguard plus 500 micro molar MIV-150 vs Carraguard and the placebo hydroxymethyl cellulose, HMC) is effective in preventing vaginal SHIV-RT infection of macaques, we recently challenged the final sets of animals (affording us 7 animals in each major test group for the 103 TCID50 challenge, for stronger datasets). Using recycled animals (animals uninfected from earlier challenges), we have also tested the ability of the MIV-150 alone (in HMC) for its anti-viral effects, as proof of concept that a NNRTI can act when applied vaginally. A single dose of 500 micro molar MIV-150 in HMC given 30min prior to a 104 TCID50 challenge had minimal impact on infection (2/2 infected). Whereas, applying the gel the day before, the day of, and the day after a 104 TCID50 virus challenge reduced infection. 3 of 7 animals became infected with a typical viremia, one remained uninfected, and 3 exhibited low-level infection with 2100 copies/ml peak viral loads (undetectable over time). Anti-CD8 treatment of these animals (approximately 5 months later) did not reveal a "controlled" infection (no virus spike in the plasma), suggesting that the low-level infections had been cleared. Testing the lower 103 TCID50 inoculum, we confirmed that 2 of 3 animals remained uninfected after receiving MIV-150 in HMC 30min prior to a 103 TCID50 challenge. Additional animals that received the 500 micro molar MIV-150 in HMC 30min prior to challenge with 103 TCID50 of SHIV-RT were just challenged to complete the comparisons to the Carraguard vs PC-817 treated animals.