Nanogel antigenic protein-delivery system for adjuvant-free intranasal vaccines.

Autor: Nochi T; Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan., Yuki Y, Takahashi H, Sawada S, Mejima M, Kohda T, Harada N, Kong IG, Sato A, Kataoka N, Tokuhara D, Kurokawa S, Takahashi Y, Tsukada H, Kozaki S, Akiyoshi K, Kiyono H
Jazyk: angličtina
Zdroj: Nature materials [Nat Mater] 2010 Jul; Vol. 9 (7), pp. 572-8. Date of Electronic Publication: 2010 Jun 20.
DOI: 10.1038/nmat2784
Abstrakt: Nanotechnology is an innovative method of freely controlling nanometre-sized materials. Recent outbreaks of mucosal infectious diseases have increased the demands for development of mucosal vaccines because they induce both systemic and mucosal antigen-specific immune responses. Here we developed an intranasal vaccine-delivery system with a nanometre-sized hydrogel ('nanogel') consisting of a cationic type of cholesteryl-group-bearing pullulan (cCHP). A non-toxic 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 after its release from the cCHP nanogel. Vigorous botulinum-neurotoxin-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 with cCHP nanogel induced strong tetanus-toxoid-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.
Databáze: MEDLINE