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-γ 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.

中文翻译：

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氧化还原反应性可生物降解的聚阳离子聚（酰胺胺）用作鼻内疫苗输送系统

诸如聚乙烯亚胺和壳聚糖的聚阳离子由于其渗透增强作用而被广泛用作粘膜疫苗递送系统。优选地，对环境敏感的可生物降解的聚阳离子将是用于粘膜疫苗递送的更好的载体材料。基于二硫键的氧化还原敏感的聚阳离子可以响应更高的细胞内谷胱甘肽浓度并通过二硫键的断裂而在细胞质中降解，这特别适合于抗原递送。在这项工作中，我们评估了氧化还原敏感的，可生物降解的聚阳离子聚（酰胺基胺）（PAA）作为粘膜疫苗载体的潜力。从以卵清蛋白作为模型蛋白抗原的初步研究发现，PAA可以通过静电吸引作用与蛋白抗原复合并包裹蛋白抗原，通过树突状细胞系DC2.4增强抗原对细胞的摄取，延长抗原在鼻腔中的停留时间，并促进抗原渗透到鼻粘膜下层。此外，用PAA递送的H7N9流感病毒重组血凝素（HA）抗原蛋白对Balb / c小鼠进行鼻内免疫。PAA / HA制剂可显着诱导更强的全身性IgG应答和粘膜IgA应答，更高的脾细胞增殖活性，更高的脾细胞分泌的细胞因子IFN-γ和IL-4分泌水平，更多的记忆CD4⁺和CD8 ⁺ T细胞，以及更多表达MHC II分子的DC。从结果来看，氧化还原反应性聚阳离子PAA作为疫苗载体有助于引发更有效的细胞和体液免疫反应。特别地，与先前报道的载体材料相比，PAA诱导了更高的细胞免疫应答。可以将智能PAA开发为用于临床应用的有效粘膜疫苗输送系统。