Adjuvants strategies for injectable and mucosal subunit vaccines

Vaccine adjuvants that strongly promote cellular immunity are required to facilitate the development of new and improved injectable and mucosal vaccines.  A number of strategies are being investigated by the Lavelle lab including polymeric nanoparticles and chitin derived polymers.  The role of particle size in adjuvanticity is contested but we show that particle size is critically important for the ability of particulate adjuvants to promote antigen-specific CD8+ T cells and Th1 responses.  In contrast, a broad range of particle sizes can promote antigen specific antibody responses.  A second adjuvant system based on chitin-derived polymers for vaccination by injection and nasal delivery will be described. We demonstrate that highly deacetylated chitin-derived polymers are most effective and promote cGAS-STING and NLRP3 inflammasome dependent Th1 responses.  The activation of this DNA sensing pathway was mediated through induction of mitochondrial reactive oxygen species and release of DNA, which is sensed by cGAS.  These adjuvants have unique cellular immunity promoting properties that are not shared with alum the most widely used adjuvant which supports their further investigation as candidates for inclusion in subunit vaccines for infectious diseases and cancer.