World population is predicted to reach 10 billion people by the year 2050, increasing more than 75 percent over the current population. Development of new contraceptive options is necessary to provide accessible birth control to all individuals regardless of sociological, financial, or educational limitations. Current literature implicates marketed spermicidal formulations in cervical and vaginal irritation leading to lesions and acquisition of sexually transmitted diseases. Reassessment of these spermicides by the FDA may result in increased costs or their removal from the market. New, inexpensive spermicides with improved safety and effectiveness must be developed. The long-term goal of this research proposal is the development of a marketable topical intra-vaginal contraceptive product based on an anti-sperm monoclonal antibody, S19. This mAb inhibits human sperm function and gamete interactions in vitro. During Phase I of the project, a recombinant single chain fragment variable region (scFv) miniantibody derived from S19 was engineered and shown to have the same anti-sperm reactivity as the native mAb. This scFv is termed RASA, for Recombinant Anti-Sperm Antibody. In the proposed Phase II study, we will first humanize RASA, and re-assess the immunoactivity of the new scFv. Second, we will develop an efficient, cost-effective platform for production and purification of large amounts of RASA in a bacterial or yeast expression system. Third, we will formulate the immunoactive humanized recombinant scFv with candidate intra-vaginal delivery vehicles including Novasomes, a trilamellar liposome-based vehicle, and test the activity of these RASA preparations to determine optimal formulation conditions and dosing. Finally, the stability and safety of the optimized formulation will be assessed.
Topical intra-vaginal contraceptive.
