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

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

Research output: Contribution to journalArticlepeer-review

398 Citations (Scopus)


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-™) 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.

Original languageEnglish
Pages (from-to)572-578
Number of pages7
JournalNature Materials
Issue number7
Publication statusPublished - 2010 Jul


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