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壳聚糖稳定鼻用乳剂递药系统增强针对重组四价登革抗原的体液和细胞应答反应。

Chitosan stabilized nasal emulsion delivery system for effective humoral and cellular response against recombinant tetravalent dengue antigen.

机构信息

Vaccine Immunology Laboratory, NPC Division, CSIR-Indian Institute of Chemical Technology, Hyderabad, 500007, India; Academy of Scientific and Innovative Research, CSIR-Indian Institute of Chemical Technology, Hyderabad, India.

Vaccine Immunology Laboratory, NPC Division, CSIR-Indian Institute of Chemical Technology, Hyderabad, 500007, India; Academy of Scientific and Innovative Research, CSIR-Indian Institute of Chemical Technology, Hyderabad, India.

出版信息

Carbohydr Polym. 2018 Jun 15;190:129-138. doi: 10.1016/j.carbpol.2018.02.073. Epub 2018 Feb 23.

Abstract

Nasal vaccine delivery systems are emerging alternatives to the conventional sub unit vaccine delivery systems owing to their ability to stimulate potent antigen specific humoral and cellular immune responses. Additional virtue of nasal delivery is its close proximity of immune cells to external epithelial layer which is the route of entry to pathogens. Toxicity of emulsion based vaccine delivery systems may be attributed to the presence of high quantities of surfactants used for stabilizing the emulsions. A safer approach would be to reduce physiologically unwanted surfactant burden in the emulsion to the bare limit to necessity. Oleic acid was used as oil phase due to its ability to enhance penetration of system in nasal mucosa. This emulsion was designed with the purpose that it activates the innate (TLR 4) and adaptive immune systems apart from performing its antigen delivery function. Proving the hypothesis, emulsion when immunized along with recombinant tetravalent dengue antigen has elicited a profound antigen specific humoral and cellular response. Antigen cross presenting and sustained release of antigen by emulsion is the key factor in shaping this immune response. Moreover, the dose sparing effect of emulsion has also been proven which has a crucial role in modern day vaccine delivery. This significant humoral and cellular response elicited proves the suitability of this emulsion system for enhancing the protective effect of vaccines against various intracellular pathogens.

摘要

鼻腔疫苗输送系统由于其能够刺激有效的抗原特异性体液和细胞免疫应答,因此是传统亚单位疫苗输送系统的新兴替代品。鼻腔给药的另一个优点是,免疫细胞与外部上皮层非常接近,而外部上皮层是病原体进入的途径。基于乳剂的疫苗输送系统的毒性可能归因于用于稳定乳剂的大量表面活性剂的存在。更安全的方法是将乳剂中的生理上不需要的表面活性剂负担减少到最低限度。由于油酸能够增强系统在鼻黏膜中的穿透能力,因此将其用作油相。设计这种乳液的目的是除了发挥其抗原传递功能外,还可以激活先天(TLR4)和适应性免疫系统。通过证明假设,与重组四价登革热抗原一起免疫时,乳剂会引起深刻的抗原特异性体液和细胞反应。乳剂的抗原交叉呈递和抗原的持续释放是形成这种免疫反应的关键因素。此外,还证明了乳剂的剂量节约效应,这在现代疫苗输送中起着至关重要的作用。这种显著的体液和细胞反应证明了该乳液系统能够增强疫苗对各种细胞内病原体的保护作用。

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