Development of a bioadhesive vaginal film for extended release of MPT antibodies

Project Summary Products which offer protection from unintended pregnancy and sexually transmitted disease infection are desired by women. This project will develop an antibody-based extended release (ER) multipurpose technology (MPT) vaginal film that combines a contraceptive monoclonal antibody (mAb) and mAbs against HIV and HSV. The ER MPT film developed will provide contraception and antiviral protection for 7 days following a single intravaginal administration. This versatile extended release MPT film platform is intended to provide a discreet, low cost and convenient alternative to women at high risk of HIV/HSV infection and unintended pregnancy. In separate Phase 1 clinical studies fast release films containing either a human contraceptive antibody (HCA) (ZB06) or mAbs against HIV and HSV (MB66) showed vaginal application of the mAbs to be safe and well tolerated. Antiviral and contraceptive efficacy was also demonstrated through ex vivo challenge of vaginal samples with either HIV, HSV, or sperm. Development of a film which combines these actives in an extended- release platform would provide a desirable option for women seeking protection. Recent data from our lab shows that vaginal films can be designed to sustain delivery of actives even in the context of menses and sexual intercourse. Using this knowledge and our expertise in the development of intravaginal films, this proposal will develop a film platform for sustained delivery of HCA and antiviral mAbs for at least 1 week. Our group recently engineered multivalent variants of these antibodies and have demonstrated that multivalent HCA has greatly enhanced contraceptive activity; we will test the activity of multivalent anti-HIV and HSV mAbs in the R61 phase of this project and study the stability and release of multivalent mAbs from ER films. Based on the outcome of these experiments, we will combine multivalent or IgG1 forms of HCA and antiviral mAbs in an ER vaginal MPT film product within the R33 phase of this project. The lead prototype ER MPT film will be fully characterized, and safety, antiviral/contraceptive activity and large-scale manufacturing feasibility will be established. Successful completion of this project will produce a versatile, low cost, and extended release vaginal MPT film for co-delivery of highly potent contraceptive, anti-HIV, and anti-HSV mAbs which is positioned for advancement to clinical evaluation. This work will generate a novel extended release MPT film platform that can be applied to other drug combinations.