LB/CV-N AND RC101 PRIMATE TESTING

University Of Washington, Seattle WA

Investigators

Linked publications & trials

Abstract

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. In order to prevent the ongoing spread of HIV and other STDs, it is imperative that an effective topical microbicide product be developed and made available for use. This project proposes to develop a combination topical microbicide product, targeted primarily at preventing the transmission of HIV, and also have activity in preventing other STDs. The product will be made up of novel compounds (a peptide and a fusion inhibitor) which exert synergistic effects on one another, thereby attacking pathogens from as many angles as possible, while preserving the integrity and microflora populations of the rectal and vaginal environments. Product formulation is guided by iterative safety, toxicity and efficacy assays (in vitro, ex vivo and in vivo). Our macaque model is used to determine the most feasible and effective delivery mechanisms, compound availability and product safety. These experiments in the macaque model are essential in filling the gap between laboratory and clinical studies. A total of twelve animals have been assigned to this project. Six have been utilized to assess the peptide development studies (RC101, a retrocyclin). Studies designed to investigate the feasibility of delivering this compound in a vaginal film formulation have been conducted. Vaginal safety studies were conducted as well. Further studies of retrocyclin-formulated films, designed to document the intravaginal presence and dispersal of active retrocyclin compound are planned. The remaining six animals have been utilized to assess the fusion inhibitor compound, cyanovirin (CV-N), being delivered by CV-N expressing lactobacilli. To date, we have conducted preliminary studies designed to investigate the most effective delivery system for cyanovirin. After delivery of lactobacilli which are capable of expressing CV-N (in vitro), we will detect CV-N presence in cervicovaginal secretions, as evidence that the CV-N can be successfully expressed in situ.