β-Glucan microparticles are good candidates for mucosal antigen delivery in oral vaccination

免疫系统 抗原 卵清蛋白 分泌成分 免疫学 佐剂 TLR2型 抗原呈递 T细胞 生物 抗体 抗原提呈细胞 过继性细胞移植 先天免疫系统
作者
R. De Smet,Tine Demoor,Stéphanie Verschuere,Mélissa Dullaers,Gary R. Ostroff,Georges Leclercq,Liesbeth Allais,Charles Pilette,Marijke Dierendonck,Bruno G. De Geest,Claude Cuvelier
出处
期刊:Journal of Controlled Release [Elsevier BV]
卷期号:172 (3): 671-678 被引量:146
标识
DOI:10.1016/j.jconrel.2013.09.007
摘要

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.
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