BLOCKING VIRUS SPREAD BY DCS WITH CARRAGEENAN-BASED COMPOUNDS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 为了完成证明PC-817（Carraguard加500微摩尔MIV-150 vs Carraguard和安慰剂羟甲基纤维素，HMC）有效预防猕猴阴道SHIV-RT感染的试验，我们最近对最后一组动物进行了攻击（对于更强的数据集，每个主要试验组中有7只动物进行了103 TCID 50攻击）。使用回收的动物（未从早期挑战中感染的动物），我们还测试了MIV-150单独（在HMC中）的抗病毒作用的能力，作为NNRTI在阴道应用时可以起作用的概念证明。在104 TCID 50攻毒前30分钟单次给予500微摩尔MIV-150的HMC溶液对感染的影响极小（2/2例感染）。然而，在104 TCID 50病毒攻击的前一天、当天和后一天应用凝胶减少了感染。7只动物中有3只感染了典型的病毒血症，1只未感染，3只表现出低水平感染，峰值病毒载量为2100拷贝/ml（随时间推移无法检测到）。这些动物的抗CD 8治疗（约5个月后）未显示“受控”感染（血浆中无病毒峰），表明低水平感染已被清除。检测较低的103 TCID 50接种物，我们证实在103 TCID 50攻毒前30分钟接受HMC中的MIV-150后，3只动物中有2只未感染。在用103 TCID 50的SHIV-RT攻毒前30分钟接受HMC中500微摩尔MIV-150的其他动物仅进行攻毒，以完成与Carraguard与PC-817给药动物的比较。

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.