Title: Design Considerations for a Sustained Release Platform to Improve Vaccine Responses

Abstract: Vaccines eliciting rapid, potent, and durable immune responses remain elusive. While successful vaccine strategies rely on the design of vaccine components, delivery technologies are key contributors to vaccine potency, quality, and durability. In the Appel Lab, we have engineered injectable polymer-nanoparticle (PNP) hydrogels to achieve sustained co-delivery of vaccines. There remains a need to explore the potential design space of PNP hydrogels in the context of clinically relevant vaccine characteristics. Such characteristics include the physicochemical identity of vaccine cargo, dose regimen, and route of administration. In the first half of my thesis, I present the use of the PNP hydrogel system for regimen compression of an inactivated virion-based clinical rabies vaccine. In the second half of my thesis, I report the compatibility of our hydrogel system across multiple administration routes, including subcutaneous and intramuscular administration, in a SARS-CoV-2 model. Overall, I demonstrate the versatility of the PNP hydrogel to improve vaccine immune responses and address current shortcomings of vaccine strategies. 

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