β-Glucan microparticles are good candidates for mucosal antigen delivery in oral vaccination
β-Glucan microparticles are good candidates for mucosal antigen delivery in oral vaccination
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DOI：
10.1016/j.jconrel.2013.09.007
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发表时间：
2013-12-28
影响因子：
10.8
通讯作者：
Cuvelier, Claude A.
中科院分区：
文献类型：
--
作者：
De Smet, Rebecca;Demoor, Tine;Cuvelier, Claude A.
不断改进口服疫苗的开发过程和功效对于对抗肠道病原体至关重要。应用安全、可生物降解和非复制的抗原递送系统的一种有前途的疫苗接种策略引起了人们越来越多的兴趣，以引发细胞和体液免疫反应。目前的研究评估了 β-葡聚糖颗粒（GP）作为口服抗原递送系统的潜力及其佐剂特性。 GP 被人肠上皮细胞系（Caco-2 和 HT-29 细胞）有效内化，而不会对细胞活力产生负面影响。 GP 通过激活的 Caco-2 细胞和 HT-29 细胞中的 CCL20 触发促炎细胞因子 IL-23p19、IL-8 以及 β-葡聚糖受体 dectin-1 和 TLR2 的表达。相比之下，口服耐受的重要介质TGF-β的表达水平在HT-29细胞中显着下调。此外，过继转移实验显示，卵清蛋白（OVA）特异性CD4（+）T细胞主要在GP-OVA喂养小鼠的脾脏中增殖。此外，我们检测到抗原再刺激后，GP-OVA 喂养的小鼠脾脏中 IL-17 显着增加，并且 IFN-γ 产生增加的趋势。口服 GP-OVA 会增加肠液中 OVA 特异性 IgA、分泌型 IgA (S-IgA) 和分泌成分 (SC) 的产生。我们的数据显示，GP 载体能够通过口服途径递送 OVA，从而在适应性免疫激活的同时实现有效的抗原呈递，从而产生 Th17 偏向的反应并产生 OVA 特异性 IgA、分泌型 IgA 和分泌成分抗体。 (C) 2013 Elsevier B.V. 保留所有权利。
Continuously improving the developmental process and the efficacy of oral vaccines is essential in the fight against intestinal pathogens. A promising strategy for vaccination applying safe, biodegradable and non-replicating antigen delivery systems has gained increased interest for eliciting cellular and humoral immune responses. The current study evaluates the potential of beta-glucan particles (GP) as an oral antigen delivery system and their adjuvant characteristics. GP are efficiently internalized by human intestinal epithelial cell lines (Caco-2 and HT-29 cells), without exerting negative effects on cell viability. GP triggered the expression of pro-inflammatory cytokines IL-23p19, IL-8 and the beta-glucan receptors dectin-1 and TLR2 by activated Caco-2 cells, and CCL20 in HT-29 cells. In contrast, the expression level of TGF-beta, an important mediator of oral tolerance, was significantly downregulated in HT-29 cells. Additionally, adoptive transfer experiments showed proliferating ovalbumin (OVA)-specific CD4(+) T cells mainly in the spleens of GP-OVA-fed mice. Furthermore, we detected a significantly increased IL-17 and a trend towards increased IFN-gamma production in the spleen of GP-OVA-fed mice upon antigen restimulation. Oral administration of GP-OVA induced increased OVA-specific IgA, secretory-IgA (S-IgA) and secretory component (SC) production in intestinal fluids. Our data show that GP vehicles are able to deliver OVA via an oral route allowing efficient antigen presentation alongside adaptive immune activation, resulting in a Th17-biased response and the production of OVA-specific IgA, secretory-IgA and secretory component antibodies. (C) 2013 Elsevier B. V. All rights reserved.