Modulating Adjuvant Release Kinetics From Scaffold Vaccines to Tune Adaptive Immune Responses

Increasing the potency, quality, and durability of vaccines represents a major public health challenge. A critical parameter that shapes vaccine immunity is the spatiotemporal context in which immune cells interact with antigen and adjuvant. While various material-based strategies demonstrate that extended antigen release enhances both cellular and humoral immunity, the effect of adjuvant kinetics on vaccine-mediated immunity remains incompletely understood. Here, a previously characterized mesoporous silica rod (MPS) biomaterial vaccine is used to develop a facile, electrostatics-driven approach to tune in vivo kinetics of the TLR9 agonist cytosine phosphoguanosine oligodeoxynucleotide (CpG). It is demonstrated that rapid release of CpG from MPS vaccines, mediated by alterations in MPS chemistry that tune surface charge, generates potent cytotoxic T cell responses and robust, T helper type 1 (Th1)-skewed IgG2a/c antibody titers. Immunophenotyping of lymphoid organs after MPS vaccination with slow or fast CpG release kinetics suggests that differential engagement of migratory dendritic cells and natural killer cells may contribute to the more potent responses observed with rapid adjuvant release. Taken together, these findings suggest that vaccine approaches that pair sustained release of antigen with rapid release of adjuvants with similar characteristics to CpG may drive particularly potent Th1 responses.