A Regimen Compression Strategy for Commercial Vaccines Leveraging an Injectable Hydrogel Depot Technology for Sustained Vaccine Exposure

Abstract

Equitable global access to vaccines requires overcoming challenges associated with complex immunization schedules and their associated economic burdens that hinder delivery in under-resourced environments. The rabies vaccine, for example, requires multiple immunizations for effective protection and each dose is cost prohibitive, and therefore inaccessibility disproportionately impacts low- and middle-income countries. In this work, an injectable hydrogel depot technology for sustained delivery of commercial inactivated rabies virus vaccines is developed. In a mouse model, it is shown that a single immunization of a hydrogel-based rabies vaccine elicited comparable antibody titers to a standard prime-boost bolus regimen of a commercial rabies vaccine, despite these hydrogel vaccines comprising only half of the total dose delivered in the bolus control. Moreover, these hydrogel-based vaccines elicited similar antigen-specific T-cell responses and neutralizing antibody responses compared to the bolus vaccine. Notably, it is demonstrated that while the addition of a potent clinical Toll-like receptor 4 (TLR4) agonist adjuvant to the gels slightly improved binding antibody responses, inclusion of this adjuvant to the inactivated virion vaccine is detrimental to neutralizing responses. Taken together, these results suggest that these hydrogels can enable an effective regimen compression and dose-sparing strategy for improving global access to vaccines.