Testing a Fast-dissolving Tablet Containing a Recombinant Live Biotherapeutic Product, MucoCept-CVN, in the Non-human Primate Model for Colonization

OA18.04 Background: Osel developed a recombinant live biotherapeutic product, MucoCept-CVN based on human vaginal Lactobacillus jensenii expressing the HIV-1 entry inhibitor Cyanovirin-N for prevention of vaginal transmission of HIV-1. We previously reported that macaques colonized with a live bacterial preparation in hydroxyethylcellulose showed a 63% reduction of SHIVSF162P3 acquisition followed repeated vaginal challenge. We formulated MucoCept-CVN as a fast dissolving vaginal tablet, which would allow for discreet, coital-independent, female controlled use. Tablets were potent (5.8 x 1011 colony forming units (CFUs)/gram) and stable for at least one year at 4°C and 25oC. Macaques were dosed with 1 tablet or 5 tablets delivered over 5 days. We examined colonization of the MucoCept-CVN bacteria in the rhesus macaque vagina at 14 and 21 days post dosing and found that 83% were highly colonized. Methods: Fast dissolving tablet were formulated (∼110 mg in a 1 x 1.5 cm mold). Tablet friability and dissolution were tested. Stability of the product was monitored for 1 year at 4°C and 25°C and for 2 months at 37°C. A single tablet or multiple tablets were administered to 18 rhesus macaques and vaginal colonization was monitored at 14 and 21 days post dosing by culture and PCR. Results: Tablets were potent and contained 5.8 x 1011 colony forming units (CFUs)/gram. The tablets were stable 1 yr at 4°C and 25oC and for 1 month at 37°C. The tablets maintained integrity when handled and dissolved quickly. High levels of colonization ∼108 CFU/vaginal swab of colonization were achieved in 15/18 macaques by day 21 post dosing. Two macaques had lower colonization levels ∼105 CFU/swab and in one macaque bacteria were detected by PCR only. Conclusions: MucoCept-CVN can be formulated and delivered as a conventional fast dissolving tablet dosage form. Colonization was achieved in 83% of macaques. The tablets were easy to handle and stable for>1 yr. This tablet formulation can be manufactured on large scale for ease of use.