Nanogel antigenic protein-delivery system for adjuvant-free intranasal vaccines.
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.
Nochi
Tomonori
T
Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
Yuki
Yoshikazu
Y
Takahashi
Haruko
H
Sawada
Shin-ichi
S
Mejima
Mio
M
Kohda
Tomoko
T
Harada
Norihiro
N
Kong
Il Gyu
IG
Sato
Ayuko
A
Kataoka
Nobuhiro
N
Tokuhara
Daisuke
D
Kurokawa
Shiho
S
Takahashi
Yuko
Y
Tsukada
Hideo
H
Kozaki
Shunji
S
Akiyoshi
Kazunari
K
Kiyono
Hiroshi
H
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
D005782:Gels; D014612:Vaccines; D019274:Botulinum Toxins, Type A