Nanogel-based PspA nasal vaccine induces microRNA-associated protective immunity in nonhuman primates (MUC4P.834)

We previously demonstrated a cationic type of cholesteryl group-bearing pullulan based nanogel containing pneumococcal surface protein A (PspA-nanogel) induced both protective Th2-mediated Ag-specific systemic and mucosal antibody (Ab) responses and Th17 cell-mediated immunity. In this study, we examined whether PspA-nanogel nasal vaccine could induce PspA-specific protective immunity and cytokines-related miRNA expression in nonhuman primates. When cynomolgus macaques were nasally immunized with 25 μg of PspA-nanogel/dose, increased levels of Th2 cell dependent PspA-specific serum and broncho alveolar lavage fluid (BALF) IgG, and nasal wash (NW) secretory IgA (SIgA) Ab responses with elevated Th17 cell immunity were seen when compared with control macaques nasally immunized with 25 μg of PspA alone or PBS. MicroRNA (miRNA) analysis of serum and nasal tissues from these PspA-nanogel immunized macaques revealed specific elevation of miR-181a and miR-326 which have been shown to corresponding to Th2 and Th17 responses, respectively. These results suggest that these two miRNAs are also associated with non-human primate Th2 and Th17 cell responses after nasal vaccination with PspA-nanogel vaccine which accounted for the induction of protective immunity against pneumonia.