Vaginally-delivered fast-dissolving antibody tablets (FDAT) for on-demand non-hormonal contraception and...

There are limited options available for safe and effective non-hormonal contraceptives or methods that block sexually transmitted diseases such as herpes simplex virus (HSV). Direct vaginal delivery of monoclonal antibodies (mAb) represents a promising approach toward both goals, but clinical translation has been limited by the lack of convenient dosage forms that can quickly and stably deliver mAbs without mess. Here, we report the development of fast-dissolving antibody tablets (FDAT) that allow for the complete release of fully functional mAbs within seconds in vaginal fluid simulants, and within two minutes in fresh human cervicovaginal mucus ex vivo. As proof-of-concept, we developed two FDAT formulations: one for HSV8, a potent neutralizing mAb against both HSV Type 1 and 2, and a second for MM008, a unique 10-Fab anti-sperm mAb that induces sperm agglutination and inhibits progressive sperm motility with picomolar potency. In sheep studies, vaginally inserted HSV8-FDAT achieved uniform distribution in different parts of the vagina within minutes, while fully maintaining HSV8 neutralization activity. Similarly, MM008-FDAT completely eliminated all progressively motile sperm within 2 min of human semen instillation. Finally, the FDATs were stable for at least 3 months of storage at room temperature within desiccated water-impermeant foil pouches, and repeated daily application of FDATs for 7 days was safe and well tolerated in sheep. These results underscore the potentials of the FDAT platform for delivery of biologic interventions to reinforce female reproductive health.