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. We have previously demonstrated that the CCR5 agonist PSC-RANTES completely protects macaques from vaginal SHIV challenge when applied to the vagina in 1mM concentrations. However, protection is only partially protective in concentrations less than 100uM, making this a cost prohibitive approach for microbicides. To determine whether we can develop strategies for decreasing the effective dose we have added isoelectric carriers (hen egg lysozyme) and performed delayed viral challenge experiments to see if the compound could be better stabilized, or had an extended duration of effect, respectively. Unfortunately these approaches did not reduce the effective dose needed for complete protection of macaques. We are now testing additional supplemental immune modulators in combination to see if they are synergistic with PSC-RANTES in preventing vaginal SHIV transmission in a cost effective manner.
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