BLOCKING VIRUS SPREAD BY DCS WITH CARRAGEENAN-BASED COMPOUNDS

这个子项目是众多研究子项目之一

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.