title: Nanogel antigenic protein-delivery system for adjuvant-free intranasal vaccines.
abstract: 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.
authors.affiliation: Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
authors.forename: Tomonori
authors.initials: T
authors.lastname: Nochi
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Yuki
authors.forename: Haruko
authors.initials: H
authors.lastname: Takahashi
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Sawada
authors.forename: Mio
authors.initials: M
authors.lastname: Mejima
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kohda
authors.forename: Norihiro
authors.initials: N
authors.lastname: Harada
authors.forename: Il Gyu
authors.initials: IG
authors.lastname: Kong
authors.forename: Ayuko
authors.initials: A
authors.lastname: Sato
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Kataoka
authors.forename: Daisuke
authors.initials: D
authors.lastname: Tokuhara
authors.forename: Shiho
authors.initials: S
authors.lastname: Kurokawa
authors.forename: Yuko
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Hideo
authors.initials: H
authors.lastname: Tsukada
authors.forename: Shunji
authors.initials: S
authors.lastname: Kozaki
authors.forename: Kazunari
authors.initials: K
authors.lastname: Akiyoshi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kiyono
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D019274:Botulinum Toxins, Type A / Q000737:chemistry; D001921:Brain / Q000378:metabolism; D003014:Clostridium botulinum / Q000378:metabolism; D016503:Drug Delivery Systems; D005260:Female; D005782:Gels / Q000737:chemistry*; D007107:Immune System; D008422:Materials Testing; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000737:chemistry*; D036103:Nanotechnology / Q000379:methods*; D009830:Olfactory Bulb / Q000378:metabolism; D014612:Vaccines / Q000737:chemistry
chemical_list: D005782:Gels; D014612:Vaccines; D019274:Botulinum Toxins, Type A