@article{8857f13e67d24b40bdf8fedec6bc94dd,
title = "Nanogel antigenic protein-delivery system for adjuvant-free intranasal vaccines",
abstract = "Nanotechnology is an innovative method of freely controlling nanometre-sized materials1. 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 2. Here we developed an intranasal vaccine-delivery system with a nanometre-sized hydrogel ('nanogel-{\texttrademark}) 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.",
author = "Tomonori Nochi and Yoshikazu Yuki and Haruko Takahashi and Sawada, {Shin Ichi} and Mio Mejima and Tomoko Kohda and Norihiro Harada and Kong, {Il Gyu} and Ayuko Sato and Nobuhiro Kataoka and Daisuke Tokuhara and Shiho Kurokawa and Yuko Takahashi and Hideo Tsukada and Shunji Kozaki and Kazunari Akiyoshi and Hiroshi Kiyono",
note = "Funding Information: We thank J. Victor Garcia of The University of North Carolina for editing the manuscript and K. Kubota of the Institute of Medical Science, The University of Tokyo, for his technical support of the radioisotope study. We also thank A. Watanabe and K. Matsuzaki of Mercian Corporation for culturing the E. coli for preparation of BoHc/A. This work was supported by grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan, and the Ministry of Health and Labour of Japan (H.K., K.A., Y.Y.); the Global Center of Excellence Program {\textquoteleft}Center of Education and Research for Advanced Genome-Based Medicine—For Personalized Medicine and the Control of Worldwide Infectious Diseases{\textquoteright} (H.K.); a Research Fellowship of the Japan Society for the Promotion of Science (T.N.); the Research and Development Program for New Bio-industry Initiatives of the Bio-oriented Technology Research Advancement Institution (Y.Y.); and the Global Center of Excellence Program, {\textquoteleft}International Research Center for Molecular Science in Tooth and Bone Diseases{\textquoteright} (K.A., Ha.T.).",
year = "2010",
month = jul,
doi = "10.1038/nmat2784",
language = "English",
volume = "9",
pages = "572--578",
journal = "Nature Materials",
issn = "1476-1122",
publisher = "Nature Publishing Group",
number = "7",
}
