MSE PhD Prospectus Defense of Matthew Geib

Title: “Topical, Non-Hormonal, Antibody-Based Male Contraception and STI Protection”

Advisory Committee: Debroah Anderson, PhD – BU MED (Advisor); Joyce Wong, PhD – BU BME, MSE; Joerg Werner, PhD – BU ME, MSE; Joshua Kays, PhD – BU BME; Dr. Lisa Rohan, PhD - University of Pittsburgh

Abstract: Over the past 50 years, access to contraception and rights to abortion in the US has steeply risen and fallen, leading to a sharp rollback in women’s rights after the US Supreme Court’s Dobb’s decision, the repeal of the federal right to an abortion and in this decision hinted that they would like to challenge Griswold v. Connecticut, the federal right to contraception. Besides the US, individual’s access to or rights to contraception is highly limited or even unavailable in many countries. Women have historically borne nearly all responsibility for contraception, and still, most couples rely on female hormonal options. Expanding male contraceptive options could promote gender equity in contraceptive planning. Despite ongoing research, male contraceptive options have not advanced significantly in over a century, primarily focusing on hormonal or systemic solutions that often fail due to side effects similar to those of female hormonal contraceptives. A viable solution should be non-hormonal and locally acting. Our lab has developed the Human Contraceptive Antibody (HCA), a potent anti-sperm monoclonal antibody that agglutinates 100% of sperm within one minute at concentrations greater than 10 μg/mL. In a Phase 1 clinical trial, an HCA vaginal film was found to be safe and highly effective in post-coital tests. I hypothesize that an effective non-hormonal male contraceptive and prophylactic against sexually transmitted infections (STIs) can be achieved via topical delivery of anti-sperm and anti-STI antibodies to the penis. To test this hypothesis, I will develop a topically applied antibody colloid containing HCA, VRC07 (anti-HIV), and HSV8-N (anti-HSV2) in silicone personal lubricant. This approach includes: (1) optimizing the long-term stability and material properties of these antibody colloids by analyzing surfactant selection, concentration, and ratio; (2) testing the pharmacokinetic efficacy and biocompatibility using a simulated intercourse model, 3D vaginal and penile epithelial models and assays for sperm agglutination and STI neutralization; and (3) tuning antibody release dynamics by encapsulating antibodies in mucopenetrating nanoparticle solutions and mucoadhesive gels. This research will enhance the understanding of antibody encapsulation and delivery through inorganic colloidal solutions and polymeric nanoparticles, advancing non-hormonal contraception for men.