Silk Fibroin Optimization for Vaccine Delivery via Microneedle Patch

Abstract

Vaccine-loaded microneedle patches have the potential to improve vaccine efficacy and access. Increasing body of evidence suggests that microneedle vaccine delivery increases the strength and breadth of immune response due to the sustained nature of vaccine antigen release. Vaccine-loaded microneedle patches also improve vaccine thermal stability, eliminating the need for expensive cold chain technologies that limit vaccination rates. Furthermore, microneedle patches allow for painless, self-administration of vaccines, eliminating sharps waste and the need to visit healthcare clinics. Vaxess’s microneedle patches consists of a solid vaccine-loaded silk fibroin tip that prevents vaccine aggregation and improves thermal stability. Although commercial and academic sources of silk fibroin exist, creating a pure, shelf-stable, consistent silk fibroin material that does not introduce limitations in microneedle patch performance is a challenge. There is a need to systematically optimize silk fibroin parameters, particularly those that have not yet been explored, to create stable silk fibroin that can be used in microneedle patches. The goals of the thesis are 1) to produce consistent and pure silk fibroin that is shelf stable even when subject to time and temperature stresses, and 2) to optimize the performance of dried silk fibroin microneedle patches for vaccine delivery. The optimized silk fibroin material will prove critical in supporting the transition from bench scale silk fibroin and microneedle patch production to clinical manufacturing at Vaxess Technologies. Taken together, this thesis presents the first systematic optimization of silk fibroin, both as a shelf-stable intermediate product and ultimately for optimized microneedle patch applications.