Nanogel antigenic protein-delivery system for adjuvant-free intranasal vaccines.
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| 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.
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| Authors | Tomonori Nochi, Yoshikazu Yuki, Haruko Takahashi, Shin-ichi Sawada, Mio Mejima, Tomoko Kohda, Norihiro Harada, Il Gyu Kong, Ayuko Sato, Nobuhiro Kataoka, Daisuke Tokuhara, Shiho Kurokawa, Yuko Takahashi, Hideo Tsukada, Shunji Kozaki, Kazunari Akiyoshi, Hiroshi Kiyono |
| Journal | Nature materials (Nat Mater) Vol. 9 Issue 7 Pg. 572-8 (Jul 2010) ISSN: 1476-4660 [Electronic] England |
| PMID | 20562880 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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