Department of Pathology, Ghent University, De Pintelaan 185, 9000 Ghent, Belgium.
J Control Release. 2013 Dec 28;172(3):671-8. doi: 10.1016/j.jconrel.2013.09.007. Epub 2013 Sep 14.
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 β-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 β-glucan receptors dectin-1 and TLR2 by activated Caco-2 cells, and CCL20 in HT-29 cells. In contrast, the expression level of TGF-β, 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-γ 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.
不断改进口服疫苗的发展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疫苗接种策略已引起人们对诱导细胞和体液免疫反应的兴趣增加。本研究评估了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 可被人肠上皮细胞系(Caco-2 和 HT-29 细胞)有效内化,而对细胞活力没有负面影响。GP 可触发 Caco-2 细胞表达促炎细胞因子 IL-23p19、IL-8 和 β-葡聚糖受体 dectin-1 和 TLR2,并在 HT-29 细胞中表达 CCL20。相比之下,TGF-β的表达水平,一种口服耐受的重要介质,在 HT-29 细胞中显著下调。此外,过继转移实验表明,在 GP-OVA 喂养的小鼠脾脏中主要增殖卵清蛋白(OVA)特异性 CD4+T 细胞。此外,我们在 GP-OVA 喂养的小鼠脾脏中检测到 IL-17 的产生显著增加,并且 IFN-γ的产生呈增加趋势。口服 GP-OVA 可诱导肠道液中 OVA 特异性 IgA、分泌型 IgA(S-IgA)和分泌成分(SC)的产生增加。我们的数据表明,GP 载体能够通过口服途径递送 OVA,同时允许有效的抗原呈递和适应性免疫激活,导致 Th17 偏向性反应和 OVA 特异性 IgA、分泌型 IgA 和分泌成分抗体的产生。