Ragweed pollen as an oral vaccine delivery system: Mechanistic insights.
Ragweed pollen as an oral vaccine delivery system: Mechanistic insights.
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DOI：
10.1016/j.jconrel.2017.10.019
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发表时间：
2017-12-28
期刊：
影响因子：
--
通讯作者：
Gill HS
中科院分区：
文献类型：
--
作者：
Uddin MJ;Gill HS
我们最近开发了花粉粒（pg）作为口服疫苗的独特方法。广泛的化学处理确保花粉微胶囊不含过敏原，可以装载疫苗抗原。我们之前在小鼠模型中证明了口服疫苗的成功。然而，帮助被处理的pg实现这一目标的潜在机制尚未完全了解。在这项研究中，我们想了解化学处理的豚草花粉（Ambrosia elatia）对先天免疫系统的影响。肠上皮细胞、巨噬细胞和树突状细胞都是先天免疫和适应性免疫的桥梁。本研究表明，在豚草花粉的反应中，所有这些细胞释放炎症细胞因子和趋化因子。扫描电镜成像显示巨噬细胞可以吞噬豚草花粉。此外，豚草存在时，小鼠树突状细胞的活化标记CD40、CD80、CD86和MHC II类分子上调。与相同大小的聚乳酸-羟基乙酸颗粒相比，豚草花粉对细胞膜没有明显的损伤。豚草不影响肠上皮细胞的完整性。豚草花粉灌胃24 h后，在小鼠小肠上皮下区也可见到豚草花粉。我们目前的研究结果得出结论，除了运输疫苗货物外，豚草花粉壳还具有额外的免疫调节特性，有助于口服抗原有效诱导免疫反应。
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.
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