Jae Yeon Joo
BME PhD Defense Presentation

Date: 2026-03-04
Time: 1:00 PM - 3:00 PM
Location / Meeting Link: HSRB-II, N600 / https://emory.zoom.us/j/94876639698

Committee Members:
Philip Santangelo, PhD (Advisor); James Dahlman, PhD; Karmella Haynes, PhD; David Myers, PhD; Francois Villinger, DVM, PhD


Title: Development of Intravaginal mRNA-Encoded Antibodies for HIV Prevention and Non-hormonal Contraception

Abstract:
Many women face risks of HIV transmission and unintended pregnancies. Although effective prevention options exist, their real-world use is often limited by systemic side effects, adherence burdens, and limited user-controlled autonomy. Consequently, these barriers lead to inconsistent use and reduced effectiveness, underscoring a critical need for effective, safe, and accessible prevention strategies. To address these unmet needs, we present an mRNA-based multipurpose prevention technology (MPT) that uses the vaginal mucosa as an in situ bioreactor. This approach enables local expression of mRNA-encoded antibodies directly at the portal of viral entry and fertilization, reducing manufacturing complexity and high costs associated with recombinant protein prophylactics. We first focused on rationally designing mRNA constructs to drive the expression of broadly neutralizing antibodies (bnAbs) with enhanced breadth and potency against HIV in the mucosal environment. Translating these findings to a clinically relevant non-human primate model, we demonstrated that this platform confers robust protective efficacy against repeated high-dose SHIV challenges, while maintaining a favorable safety profile. Beyond viral prophylaxis, we expanded the platform’s utility to include non-hormonal contraception. We successfully engineered a dual-function formulation that co-expresses anti-HIV and anti-sperm antibodies, providing proof-of-concept for a single-dose strategy capable of simultaneous virus neutralization and sperm immobilization. Finally, we discuss future strategies to incorporate advanced polymeric nanocarriers, leveraging insights from pulmonary delivery innovations, to optimize therapeutic potency and mucosal durability for next-generation intravaginal mRNA delivery systems. Overall, these findings establish the intravaginal mRNA-encoded antibody platform as a promising, accessible solution that empowers women with comprehensive control over their reproductive health.