Vaginal Ring for Preventing Bacterial Vaginosis

DESCRIPTION (provided by applicant): Bacterial Vaginosis (BV) is an exceptionally common vaginal condition in which robust lactobacillus microflora in the vagina is replaced by a dense polymicrobial overgrowth. At any given time, about 1 in 3 women in the U.S. have BV; half are asymptomatic, and most women with symptomatic BV have only mild symptoms (increased discharge with a fishy smell). Despite these missing or mild symptoms, BV markedly increases risk of adverse birth outcomes (premature births and still births) and markedly increases risks of sexually transmitted infections (STIs). Thus BV poses a major and yet under-recognized public health problem. What causes the fluctuating instability of vaginal microflora between lactobacilli and BV is unknown. Episodes of BV can be treated transiently with antibiotics (metronidazole, clindamycin) but relapse occurs frequently. Women with BV typically have ~2 episodes per menstrual cycle. Given the markedly increased BV-associated risks, and the high prevalence of BV, there is a major unmet need for a vaginal product that will provide long-term prevention of BV especially during pregnancy and for women at high risk of STIs. Healthy vaginal lactobacilli continuously produce lactic acid at a rate that acidifies the vagina to pH~4. We recently discovered that lactic acid potently inactivates a broad range of BV-associated bacteria. The aim of this STTR application is to develop a vaginal ring that continuously releases lactic acid to prevent BV ( BVP-Ring ). The Ring will be designed to release lactic acid at a rate comparable to that produced by healthy lactobacilli and thus will not over-acidify the vagina. The Ring will provide a 'safe harbor' for lactobacilli whenever factors (e.g., menses, sexual intercourse) occur that might otherwise initiate an episode of BV. By supplying a naturally present protective agent the Ring will likely be safe and nontoxic, and there is a strong basis for expecting it to be effective: Lactic acid potently inactivates BV-associated bacteria in vitro, and vaginal gels with lactic acid, when applied frequently over many weeks, have been shown clinically to reduce BV relapse. Vaginal rings are highly user-acceptable for contraception and for hormone replacement therapy. Thus the BVP-Ring is likely to be user-acceptable, and much more acceptable than frequently applying a vaginal gel, or frequent doses of antibiotics. For STTR Phase I, Specific Aims at Johns Hopkins University are: (1) Determine the rate at which lactobacilli produce lactic acid in cervicovaginal fluid and (2) Determine the rate at which lactic acid applied to the vagina of women with BV leaves the vaginal lumen by diffusing through the vaginal epithelium. These measurements will be used to estimate the rate at which the vaginal ring should release lactic acid, The Specific Aim at ReProtect, Inc. is (3) Design a silicone BVP-Ring that releases lactic acid for 1 month at the rate determined in Aims 1 and 2, and produce prototype Rings ready to be tested in vivo in STTR Phase II. PUBLIC HEALTH RELEVANCE: Unfortunately, most women, most of the time, do not have robust vaginal lactobacilli that protect the vagina with lactic acid; at any given time about 1 in 3 women have bacterial vaginosis (BV), a condition that puts women at markedly increased risks of poor pregnancy outcomes and sexually transmitted infections. The aim of this STTR project is to develop a vaginal ring that releases lactic acid to prevent BV. The ring will likely be useful for women with frequent episodes of symptomatic BV, and especially useful for preventing BV during pregnancy. )