Hexavalent Sperm-Binding IgG Antibody Released from Self-Dissolving Vaginal Film Enables Potent, On-Demand Non-Hormonal Female Contraception
Shrestha, B.; Vincent, K.; Schaefer, A.; Zhu, Y.; Vargas, G.; Motamedi, M.; Swope, K.; Morton, J.; Simpson, C.; Pham, H.; Brennan, M. B.; Pauly, M. H.; Zeitlin, L.; Bratcher, B.; Whaley, K. J.; Moench, T. R.; Lai, S. K.
Show abstract
Non-hormonal products for on-demand contraception are a global health technology gap, motivating us to pursue the use of sperm-binding monoclonal antibodies as a strategy to enable safe, effective, desirable, on-demand contraception. Here, using cGMP-compliant Nicotiana-expression system, we produce an ultra-potent sperm-binding IgG antibody possessing 6 Fab arms per molecule that bind a well-established contraceptive antigen target, CD52g. We term this hexavalent antibody "Fab-IgG-Fab" (FIF) to reflect its molecular orientation. The Nicotiana-produced FIF exhibits at least 10-fold greater sperm agglutination potency and kinetics than the parent IgG, while preserving Fc-mediated trapping of individual spermatozoa in mucus. We formulate the Nicotiana-produced FIF into a polyvinyl alcohol-based water-soluble contraceptive film, and evaluate its potency in reducing progressively motile sperm in the sheep vagina. Two minutes after vaginal instillation of human semen, no progressively motile sperm are recovered from the vaginas of sheep receiving FIF-Film. In contrast, high numbers of progressively motile sperm are recovered from sheep receiving a placebo film control. Our work supports the potential of highly multivalent contraceptive antibodies to provide safe, effective, on-demand non-hormonal contraception.
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