The M Cell-Targeting Ligand Promotes Antigen Delivery and Induces Antigen-Specific Immune Responses in Mucosal Vaccination
The M Cell-Targeting Ligand Promotes Antigen Delivery and Induces Antigen-Specific Immune Responses in Mucosal Vaccination
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DOI：
10.4049/jimmunol.0903184
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发表时间：
2010-11-15
影响因子：
4.4
通讯作者：
Jang, Yong-Suk
中科院分区：
文献类型：
--
作者：
Kim, Sae-Hae;Seo, Ki-Weon;Jang, Yong-Suk
口腔粘膜免疫可在全身区室和粘膜中诱导保护性免疫。成功的粘膜免疫依赖于Ag递送到粘膜免疫诱导位点。粘膜内M细胞的高胞吞活性使得这些细胞成为粘膜Ag递送的有吸引力的靶点，尽管仍不清楚将Ag递送至M细胞是否仅能保证诱导有效的免疫应答。在这项研究中，我们评估了具有佐剂活性的M细胞靶向配体诱导针对配体融合Ag的免疫的能力。我们通过对体外分化的M样细胞的噬菌体展示文库进行生物淘选来选择M细胞靶向配体，并使用模型Ag产生与所选配体融合的重组Ag。所选的肽配体之一，Co 1，促进了配体融合的Ag与小鼠派尔集合淋巴结M细胞和人M样细胞的结合，这些细胞已经通过与M细胞特异性抗体和抗GP 2抗体的结合来定义。此外，Co 1配体增强了免疫原性组织在离体环测定和体内口服给药实验中对融合Ag的摄取。口服给药后，与不含配体的对照Ag相比，配体融合的Ag增强了针对融合的Ag的免疫应答。此外，配体的这种使用支持针对融合Ag的偏斜的Th 2型免疫应答。总的来说，这些结果表明，通过生物淘选针对培养的M样细胞的配体可以用作佐剂，用于靶向Ag递送到粘膜免疫系统中以增强免疫诱导。免疫学杂志，2010，185：5787-5795。
Oral mucosal immunization can induce protective immunity in both systemic compartments and the mucosa. Successful mucosal immunization depends on Ag delivery to the mucosal immune induction site. The high transcytotic activity of M cells within the mucosa makes these cells attractive targets for mucosal Ag delivery, although it remains unclear whether delivery of Ag to M cells only can guarantee the induction of effective immune responses. In this study, we evaluated the ability of an M cell-targeting ligand with adjuvant activity to induce immunity against ligand-fused Ag. We selected M cell-targeting ligands through biopanning of a phage display library against differentiated in vitro M-like cells and produced the recombinant Ags fused to the selected ligands using the model Ag. One of the selected peptide ligands, Co1, promoted the binding of ligand-fused Ag to mouse Peyer's patch M cells and human M-like cells that had been defined by binding with the M cell-specific and anti-GP2 Abs. In addition, Co1 ligand enhanced the uptake of fused Ag by immunogenic tissue in an ex vivo loop assay and in vivo oral administration experiments. After oral administration, the ligand-fused Ag enhanced immune responses against the fused Ag compared with those of the control Ag without ligand. In addition, this use of the ligand supported a skewed Th2-type immune response against the fused Ag. Collectively, these results suggest that the ligand selected through biopanning against cultured M-like cells could be used as an adjuvant for targeted Ag delivery into the mucosal immune system to enhance immune induction. The Journal of Immunology, 2010, 185: 5787-5795.