中文摘要：本研究评价了氧化反应敏感的、可生物降解的阳离子聚（酰氨基胺）（PAA）作为粘膜疫苗载体的潜力。以卵清蛋白作为蛋白抗原的模型中，PAA可以通过静电吸引与蛋白抗原形成复合物并包裹在其表面，从而增强树突状细胞DC2.4内抗原的获取能力，延长鼻腔内抗原的持续时间，促进抗原向鼻粘膜下层渗入。试验还以Balb/c小鼠为试验对象，采用PAA传递的重组H7N9流感病毒HA抗原蛋白进行鼻内免疫。结果表明，PAA/HA复合物能够显著诱导产生有效的全身IgG反应和粘膜IgA反应，更高的脾细胞增殖活性、脾细胞IFN-γ和IL-4分泌水平、CD4(+) 和CD8(+) T 细胞水平、以及树突状细胞（DCs）表达的MHC II分子水平。由以上结果可知，将氧化反应阳离子聚PAA用作疫苗载体有利于激发产生更多的细胞和体液免疫反应；特别是，与已有的疫苗载体材料相比，PPA能够诱导产生更多的细胞免疫反应。PPA能够作为一种有效的粘膜免疫传递系统进行临床应用开发。
 
外文摘要：Polycations such as polyethylenimine and chitosan have been widely used as mucosal vaccine delivery systems due to their permeation enhancement effect. Preferably, environmentally responding biodegradable polycations would be better carrier materials for mucosal vaccine delivery. Disulfide bond-based redox-sensitive polycations could respond to the higher intracellular glutathione concentration and degrade in the cytoplasm via the breakage of the disulfide bonds, which are particularly suitable for antigen delivery. In this work, we evaluated the potential of redox-sensitive, biodegradable polycation poly(amido amine) (PAA) as mucosal vaccine carriers. From the primary studies with ovalbumin used as a model protein antigen, it is found that PAA could complex with and encapsulate protein antigen via electrostatic attraction, enhance the cellular uptake of antigen by dendritic cell line DC2.4, prolong antigen residence in nasal cavity, and promote antigen permeation into nasal submucosal layer. Further, Balb/c mice were intranasally immunized with PAA-delivered recombinant hemagglutinin (HA) antigen protein of H7N9 influenza virus. The PAA/HA formulations induced significantly more potent systemic IgG response and mucosal IgA response, higher splenocyte proliferation activity, higher secretion levels of cytokines IFN-gamma and IL-4 by splenocytes, more memory CD4(+) and CD8(+) T cells, and more DCs expressing MHC II molecule. From the results, the redox-responsive polycation PAA as vaccine carriers helped elicit more potent cellular and humoral immune responses. Particularly, PAA induced much higher cellular immune response compared with previously reported carrier materials. The intelligent PAA could be developed as efficient mucosal vaccine delivery systems for clinical applications.
外文关键词：MUCOSAL IMMUNITY; GENE DELIVERY; GLYCOPROTEIN ANTIGENS; CELL RESPONSES; CANCER-THERAPY; ADJUVANT; POLYETHYLENEIMINE; DNA; POTENT; POLYMERS
作者：Guo, Z; Li, S; Lv, M; Liu, ZH; Xue, W
作者单位：暨南大学
期刊名称：ACS BIOMATERIALS SCIENCE & ENGINEERING
期刊影响因子：2.42
出版年份：2017
出版刊次：10
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