Injectable hydrogels, attractive for sustained vaccination due to their tissue mimicry and minimal invasiveness, have not yet achieved diverse dosing profiles essential for testing their potential in humoral immunization. We addressed this by using oxanorbornadiene (OND) linkages which react with thiol nucleophiles, triggering retro-Diels Alder fragmentation with half-lives from minutes to months. Hydrogels, made from OND-modified dextran and polyethylene glycol thiols, entrapped virus-like particles (VLPs) as vaccine models. These hydrogels were formulated for injection, and demonstrated programmable VLP release across various profiles including first-order, linear, positive-exponential, and delayed-burst over a two-week period. Safety and immune response evaluations in mouse models will next determine the suitability of these materials for investigating immune response mechanisms and enhancing single-dose vaccines.
Learning Objectives:
Learn about injectable hydrogel vaccination and understand the importance of fine-tuning the vaccine release profiles
Understand the impact of novel linker chemistry on the development of hydrogel formulations
Understand how hydrogel degradation affects vaccine cargo release