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

作者：Nochi Tomonori; Yuki Yoshikazu; Takahashi Haruko; Sawada Shin ichi; Mejima Mio; Kohda Tomoko; Harada Norihiro; Kong Il Gyu; Sato Ayuko; Kataoka Nobuhiro; Tokuhara Daisuke; Kurokawa Shiho; Takahashi Yuko; Tsukada Hideo; Kozaki Shunji; Akiyoshi Kazunari; Kiyono Hiroshi^*

来源：Nature Materials, 2010, 9(7): 572-578.

DOI：10.1038/NMAT2784

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.

• 出版日期2010-7
• 单位河北医科大学