Thermal-sensitive hydrogel as adjuvant-free vaccine delivery system for H5N1 intranasal immunization

For H5N1 influenza immunization, we developed a thermal-sensitive hydrogel as intranasal vaccine delivery system, which was formulated with N-[(2-hydroxy-3-trimethylammonium) propyl] chitosan chloride (HTCC) and α, β-glycerophosphate (α, β-GP). The flowing solution of HTCC/GP under room temperature could gelate rapidly at body temperature, which significantly prolonged the H5N1 split antigen residence time in nasal cavity. This system also enhanced the transepithelial transport via the paracellular routes due to the disorganization of ZO-1 protein in nasal epithelial tissue. In comparison to naked H5N1 split antigen and MF59 adjuvanted antigen, as designed hydrogel/H5N1 vaccine induced greater antigen-specific systemic immune responses and mucosal IgA immunity without adjuvants. Furthermore, a boosted cellular and humoral response was also obtained by examination of IFN-γ and IL-4 cytokines, respectively. In addition, hydrogel based formulation promoted the antigen-specific CD8+ T cell immune memory as determined by the proportion of central and effector memory CD8+ T cells in nasal associated lymphoid tissue (NALT). These results demonstrate that the HTCC hydrogel has potential as an adjuvant-free platform for H5N1 split antigen intranasal vaccination.