To improve current mucosal allergen immunotherapy Vibrio cholerae neuraminidase (NA) was evaluated as a novel epithelial targeting molecule for functionalization of allergen-loaded, poly(D,L-lactide-co-glycolide) (PLGA) microparticles (MPs) and compared to the previously described epithelial targeting lectins wheat germ agglutinin (WGA) and Aleuria aurantia lectin (AAL).

All targeters revealed binding to Caco-2 cells, but only NA had high binding specificity to α-L fucose and monosialoganglioside-1. An increased transepithelial uptake was found for NA-MPs in a M-cell co-culture model. NA and NA-MPs induced high levels of IFN-γ and IL10 in naive mouse splenocytes and CCL20 expression in Caco-2. Repeated oral gavage of NA-MPs resulted in a modulated, allergen-specific immune response. In conclusion, NA has enhanced M-cell specificity compared to the other targeters. NA functionalized MPs induce a Th1 and T-regulatory driven immune response and avoid allergy effector cell activation. Therefore, it is a promising novel, orally applied formula for allergy therapy.

为了改善目前的黏膜过敏原免疫治疗，霍乱弧菌神经氨酸酶 (NA) 被评估为一种新型上皮靶向分子，用于功能化载有过敏原的聚 (D,L-丙交酯-共-乙交酯) (PLGA) 微粒 (MPs)，并与先前描述的上皮靶向凝集素小麦胚凝集素（WGA）和金黄色葡萄球菌凝集素（AAL）。

所有靶向剂均显示与 Caco-2 细胞结合，但只有 NA 对 α-L 岩藻糖和单唾液酸神经节苷脂-1 具有高结合特异性。在 M 细胞共培养模型中发现 NA-MPs 的跨上皮摄取增加。NA 和 NA-MPs 在幼稚小鼠脾细胞中诱导高水平的 IFN-γ 和 IL10 以及在 Caco-2 中的 CCL20 表达。NA-MPs 的反复口服管饲导致调节的过敏原特异性免疫反应。总之，与其他靶向剂相比，NA 具有增强的 M 细胞特异性。NA 功能化 MP 诱导 Th1 和 T 调节驱动的免疫反应并避免过敏效应细胞活化。因此，它是一种很有前途的新型口服过敏治疗配方。