Nanogel antigen delivery system for adjuvant-free intranasal vaccines (46.16)

Abstract Nanotechnology is an innovative method of freely controlling nanometer-sized materials. The recent outbreak of mucosal infectious diseases have increased the demands for development of mucosal vaccines because they induce antigen-specific both mucosal and systemic immune responses. However because of lacking the effective antigen delivery system to aero-digestive mucosa, co-administration of mucosal adjuvant mediating protective but also undesired immunity is continuously needed. Here we developed a novel intranasal vaccine-delivery system with a nanometer-sized hydrogel (“nanogel”) consisting of a cationic type of cholesteryl group-bearing pullulan (cCHP). A nontoxic subunit fragment of Clostridium botulinum type-A neurotoxin BoHc/A administered intranasally with cCHP nanogel (cCHP-BoHc/A) continuously adhered to the nasal epithelium and was effectively taken up by mucosal dendritic cells (DCs) after its release from the cCHP nanogel. Vigorous botulinum neurotoxin A (BoNT/A)-neutralizing serum IgG and secretory IgA antibody responses were induced without co-administration of mucosal adjuvant. Importantly, intranasally administered cCHP-BoHc/A did not accumulate in the olfactory bulbs or brain. Moreover, intranasally immunized tetanus toxoid (TT) with cCHP nanogel induced strong TT-specific systemic and mucosal immune responses. These results indicate that cCHP nanogel can be used as a universal protein-based antigen-delivery vehicle for adjuvant-free intranasal vaccination.