Bhawana “Suruchi” Shrestha
Engineering Ultra-Potent Sperm-Binding IgG Antibodies for Effective Non-Hormonal Female Contraception
Nearly half of all pregnancies in the United States are unintended. Millions of women avoid using available contraceptives and risk unintended pregnancies every year, due to perceived and/or real side-effects associated with the use of exogenous hormones. This indicates a strong unmet need for alternative, non-hormonal contraceptives. Direct vaginal delivery of sperm-binding monoclonal antibodies (mAb) can provide the much-needed non-hormonal contraception. To address the unmet need, this project developed a panel of ultra-potent sperm-binding IgGs possessing 6-10 Fabs against a unique surface antigen universally present on human sperm. These highly multivalent IgGs (HM-IgGs) are at least 10- to 16-fold more potent and faster at agglutinating sperm than the parent IgG, while preserving Fc-mediated trapping of individual spermatozoa in vaginal mucus. The increased potencies translate to effective (>99.9%) reduction of progressively motile sperm in the sheep vagina using just 33 micrograms of the 10-Fab HMIgG. HM-IgGs produce at comparable yields and possess identical thermal stability to the parent IgG, with greater homogeneity. HM-IgGs represent not only promising biologics for non-hormonal contraception but also a promising platform for generating potent agglutinating mAb for diverse medical applications.
At the start of my PhD, I had no prospects of competing for prestigious fellowships because international graduate students are typically ineligible for fellowships and awards. By changing the eligibility criteria, the PhRMA Foundation gave me an opportunity to attain a professional achievement that makes me a strong candidate for a career in the pharmaceutical industry. I am extremely honored to be a recipient of the PhRMA Foundation Predoctoral Fellowship in Pharmaceutics. This fellowship has provided me the financial freedom and confidence to solely focus on advancing my dissertation research and has resulted in multiple first-author research manuscripts.