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Ragweed pollen as an oral vaccine delivery system: Mechanistic insights
Journal of Controlled Release ( IF 10.8 ) Pub Date : 2017-10-17 , DOI: 10.1016/j.jconrel.2017.10.019
Md Jasim Uddin , Harvinder Singh Gill

We have recently developed pollen grains (PGs) as a unique method to deliver vaccines orally. Extensive chemical processing ensures allergen-free pollen microcapsules that can be loaded with vaccine antigens. Successful oral vaccine delivery has been previously demonstrated by us in a mouse model. However, the underlying mechanisms that help the processed PGs to achieve this goal were not fully understood. In this study, we wanted to understand the effects of chemically processed ragweed pollen (Ambrosia elatior) on the innate immune system. Intestinal epithelial cells, macrophages, and dendritic cells all bridge the innate and adaptive immunity. This study has shown that in response to ragweed pollen all these cells release inflammatory cytokines and chemokines. Scanning electron microscopy imaging revealed that macrophages can engulf ragweed pollen. In addition, in the presence of ragweed, mouse dendritic cells upregulated their activation markers, that is, CD40, CD80, CD86, and MHC class II molecules. Ragweed pollens did not cause significant cell membrane damage as compared to similarly sized poly (lactic-co-glycolic acid) particles. Moreover, ragweed did not affect the integrity of the intestinal epithelial cells. Ragweed pollens were also found in the subepithelial region of the small intestine 24 h after pollens were gavaged to mice. Our current findings lead to the conclusion that besides transporting the vaccine cargo, ragweed pollen shells have additional immunomodulatory properties that help the orally delivered antigen to effectively induce an immune response.



中文翻译:

豚草花粉作为口服疫苗输送系统:机理的见解

最近,我们开发了花粉粒(PGs)作为口服疫苗的独特方法。广泛的化学处理过程确保了无过敏原的花粉微胶囊可以装载疫苗抗原。我们先前已经在小鼠模型中证明了成功的口服疫苗递送。但是,帮助加工过的PG实现此目标的基本机制尚未完全了解。在这项研究中,我们想了解化学加工豚草花粉(Ambrosia elatior)关于先天免疫系统。肠上皮细胞,巨噬细胞和树突状细胞都桥接先天和适应性免疫。这项研究表明,针对豚草花粉,所有这些细胞均释放出炎性细胞因子和趋化因子。扫描电子显微镜成像显示巨噬细胞可以吞噬豚草花粉。此外,在豚草的存在下,小鼠树突状细胞上调了它们的激活标记,即CD40,CD80,CD86和MHC II类分子。相比于类似尺寸的聚豚草花粉没有造成显著细胞膜损伤(乳酸--乙醇酸)颗粒。此外,豚草不影响肠上皮细胞的完整性。在向小鼠喂食花粉后24小时,在小肠的上皮下区域也发现了豚草花粉。我们目前的发现得出的结论是,豚草花粉壳除了运输疫苗货物外,还具有其他免疫调节特性,有助于口服递送的抗原有效诱导免疫反应。

更新日期:2017-10-17
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