一种新型的纳米凝胶-不需其他辅助剂的鼻腔给药抗原蛋白疫苗载体中英..docxVIP

20 JUNE 2010Nature Matreials Nanogel antigenic protein-delivery system for adjuvant-free intranasal vaccinesNanotechnology is an innovative method of freely controlling nanometre-sized materials1. Recent outbreaks of mucosal infectious diseases have increased the demands for devel- opment of mucosal vaccines because they induce both sys- temic and mucosal antigen-specific immune responses2. 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 adju- vant. Importantly, intranasally administered cCHP–BoHc/A did not accumulate in the olfactory bulbs or brain. Moreover,intranasally immunized tetanus toxoid with cCHP nanogel in- duced strong tetanus-toxoid-specific systemic and mucosal im- mune responses. These results indicate that cCHP nanogel can be used as a universal protein-based antigen-delivery vehicle for adjuvant-free intranasal vaccination.题目：一种由纳米凝胶构成的新型抗原蛋白疫苗传递系统---通过鼻腔给药而无需要其他辅佐剂摘要：作为一种新手段，纳米技术可以生产纳米级的新材料。最近爆发的粘膜传染疾病会引起全身性以及粘膜特异的免疫应答。因此，粘膜抗体对人类的健康是至关重要的。这里，我们研究了一种新型的疫苗传递系统，这是一种由带正离子的胆甾醇基和支链淀粉构成的纳米级凝胶(cCHP)。一种无毒的蛋白片段---肉毒杆菌神经毒素A抗原疫苗Hc (BoHc/A)与cCHP纳米凝胶一起通过鼻腔给药方式粘附到鼻腔粘膜上皮细胞，BoHc/A从cCHP纳米凝胶中释放后有效地进入了粘膜的树突状细胞并且引起强烈的IgG、IgA免疫应答。这种免疫反应并不需要其他的辅助剂。更重要的是，鼻腔给药的cCHP–BoHc/A并不会在嗅球或者大脑中积累。此外，用这种纳米凝胶载体制作的破伤风疫苗也获得了特异的全身性免疫应答反应。这些结果显示cCHP可以作为一种普遍的蛋白抗原传递载体，用作生产无其他辅助剂的鼻腔给药疫苗。Beginning in 2003, an enormous research initiative—Grand Challenges in Global Health—has been organized worldwide with the support of the Bill and Melinda Gates Founda