Nanogel antigenic protein-delivery system for adjuvant-free intranasal vaccines
Nanogel antigenic protein-delivery system for adjuvant-free intranasal vaccines
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DOI：
10.1038/nmat2784
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发表时间：
2010-07-01
期刊：
影响因子：
41.2
通讯作者：
Kiyono, Hiroshi
中科院分区：
文献类型：
--
作者：
Nochi, Tomonori;Yuki, Yoshikazu;Kiyono, Hiroshi
纳米技术是一种自由控制纳米材料的创新方法（1）。最近爆发的粘膜感染性疾病增加了开发粘膜疫苗的需求，因为它们诱导全身和粘膜抗原特异性免疫应答（2）。在这里，我们开发了一种鼻内疫苗递送系统与纳米大小的水凝胶（“纳米凝胶”）组成的阳离子型的胆固醇基轴承支链淀粉（cCHP）。肉毒梭菌A型神经毒素BoHc/A的无毒亚基片段与cCHP纳米凝胶鼻内给药（cCHP-BoHc/A）持续粘附于鼻上皮，并且在其从cCHP纳米凝胶释放后被粘膜树突状细胞有效摄取。强有力的肉毒杆菌神经毒素A中和血清IgG和分泌型伊加抗体反应诱导没有共同管理的粘膜佐剂。重要的是，鼻内给药的cCHP-BoHc/A不会在嗅球或大脑中积累。此外，用cCHP纳米凝胶鼻内免疫破伤风类毒素诱导强的破伤风类毒素特异性全身和粘膜免疫应答。这些结果表明，cCHP纳米凝胶可用作用于无佐剂鼻内疫苗接种的通用的基于蛋白质的抗原递送载体。
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.