Phase 1 Randomized Double-Blind Placebo-Controlled Safety Study of MucoCept-CVN (Lactobacillus jensenii 1153-1666) Administered Vaginally to Healthy Women - MUCOCEPT-CVN: ABSTRACT Women bear the brunt of the HIV epidemic. Thus, female-initiated prevention methods including live biotherapeutic products (LBPs) are urgently needed to help curtail the HIV epidemic worldwide. The vaginal mucosa is densely populated with commensal bacteria dominated by Lactobacillus strains that play a critical role in the maintenance of vaginal health. The loss of lactobacilli leads to vaginal dysbiosis, and an increased risk of heterosexual transmission of HIV and other sexually transmitted infections (STIs). MucoCept-CVN contains Lactobacillus jensenii 1153-1666, a natural component of the human vaginal microbiota that has been bioengineered into a recombinant vaginally administered LBP which continuously expresses the potent HIV entry inhibitor modified-cyanovirin-N (mCV-N) right at the site of infection. Preclinical studies have been completed and showed a 63% reduction in simian/HIV (SHIV) transmission after repeated vaginal challenges of macaques treated with L. jensenii 1153-1666 compared to placebo. We propose a first-in-human Phase 1 randomized, placebo-controlled study of one and three doses of vaginally administered MucoCept-CVN in 12 women. The study is designed to collect critical data needed to advance the clinical development of MucoCept- CVN, specifically (1) understanding factors that influence vaginal colonization by L. jensenii 1153-1666, including dose and endogenous vaginal microbiota; and (2) pharmacokinetic, tissue and systemic effects of L. jensenii 1153-1666, such as adverse events (AE) and findings in colposcopy and vaginal biopsy, and (3) changes to the vaginal microbiota. We also need to show that (4) L. jensenii 1153-1666 can be sufficiently cleared with antibiotics should the need arise for rescue therapy. As a long-acting, self-generating LBP with a low risk of significant adverse events, MucoCept-CVN has characteristics that should translate to high acceptability and excellent adherence. In addition, MucoCept-CVN is cost-effective and has promise as a potential multipurpose prevention technology to avert other genital tract infections. Research to date is proof- of-concept that MucoCept-CVN may be safe and lead to a significant reduction in female HIV acquisition. The proposed research is a critical step toward a safe, effective, durable, self-renewing, coitally independent, potentially multi-purpose prevention product for women that promotes vaginal health and provides protection from HIV and potentially other STIs.
