Bridging Systemic Immunity with Gastrointestinal Immune Responses via Oil‐in‐Polymer Capsules,Advanced Materials

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Bridging Systemic Immunity with Gastrointestinal Immune Responses via Oil‐in‐Polymer Capsules
Advanced Materials ( IF 27.4 ) Pub Date : 2018-06-12 , DOI: 10.1002/adma.201801067
Yufei Xia _{1,

2} , Jie Wu _{1,

3} , Yiqun Du ₄ , Chunyu Miao ₁ , Zhiguo Su _{1,

3,

5} , Guanghui Ma _{1,

3,

5}

Affiliation

As peripheral lymphocytes are typically excluded from the gastrointestinal lymph tissues, current parenteral vaccinations fail to simultaneously induce systemic and mucosal responses. To break the natural barrier, “immunoticket” capsules are developed and heralded, which are designed with positive charged shells and oily core to spatiotemporally deliver antigens and all‐trans retinoic acid (RA). After intramuscular vaccinations, these capsules function as an immunoticket to cultivate peripheral dendritic cells (DCs) with gut‐homing receptors (CCR9). By hitchhiking on the concentration gradient of the CC‐motif chemokine ligand 25 (CCL25), the primed DCs would home to the gut associated lymphoid tissues (GALTs) and induce antigen‐specific IgA secretion and T cell engagements. Compared with the currently employed RA‐involving formulations, the immunoticket capsules stimulate enhanced RA‐mediated gut‐tropism by mounting the inflammatory innate immunity. Through controlling the RA payload, the potential regulatory T cell engagement is circumvented. In ovalbumin (OVA) and EV71 vaccinations, the immunoticket capsules induce potent serum IgG titer and antigen‐specific cytotoxic T cells in the peripheral lymph tissues, as well as robust IgA secretion and T cell engagements on gastrointestinal sites. The data suggest the potential of the immunotickets to serve as a facile, effective, and safe strategy to provide comprehensive immune responses against gastrointestinal infections and diseases

中文翻译：

通过油中聚合物胶囊弥合全身免疫与胃肠道免疫反应

由于通常从胃肠道淋巴组织中排除外周淋巴细胞，因此当前的肠胃外疫苗接种不能同时诱导全身和粘膜反应。为了打破天然屏障，开发并发布了“ immunoticket”胶囊，其设计为带正电荷的外壳和油性核，可时空递送抗原并进行全反式视黄酸（RA）。肌肉注射疫苗后，这些胶囊可作为免疫标签来培养带有肠归巢受体（CCR9）的外周树突状细胞（DC）。通过搭档CC-motif趋化因子配体25（CCL25）的浓度梯度，引发的DC将到达肠道相关淋巴组织（GALT），并诱导抗原特异性IgA分泌和T细胞参与。与目前使用的涉及RA的制剂相比，免疫票胶囊通过增加炎症性先天免疫来刺激增强的RA介导的肠道嗜性。通过控制RA有效载荷，可以避免潜在的调节性T细胞参与。在卵清蛋白（OVA）和EV71疫苗接种中，免疫门票胶囊可在外周淋巴组织中诱导有效的血清IgG滴度和抗原特异性细胞毒性T细胞，以及强大的IgA分泌和胃肠道上的T细胞结合。数据表明，免疫门票有可能作为一种简便，有效和安全的策略提供针对胃肠道感染和疾病的全面免疫反应

更新日期：2018-06-12

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