Journal
NATURE MATERIALS
Volume 9, Issue 7, Pages 572-578Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/NMAT2784
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Funding
- Ministry of Education, Culture, Sports, Science and Technology of Japan
- Ministry of Health and Labour of Japan
- Global Center of Excellence Program
- Japan Society for the Promotion of Science
- Research and Development Program for New Bio-industry Initiatives of the Bio-oriented Technology Research Advancement Institution
- International Research Center for Molecular Science in Tooth and Bone Diseases
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Nanotechnology is an innovative method of freely controlling nanometre-sized materials(1). 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-Aneutralizing 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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