Targeted oral delivery of BmpB vaccine using porous PLGA microparticles coated with M cell homing peptide-coupled chitosan
Targeted oral delivery of BmpB vaccine using porous PLGA microparticles coated with M cell homing peptide-coupled chitosan
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DOI：
10.1016/j.biomaterials.2013.11.073
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发表时间：
2014-02-01
期刊：
影响因子：
14
通讯作者：
Cho, Chong-Su
中科院分区：
文献类型：
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作者：
Jiang, Tao;Singh, Bijay;Cho, Chong-Su
M细胞是粘膜免疫诱导的关键参与者，是将疫苗有效递送至粘膜免疫组织的肠道屏障之一。为了克服这一障碍，我们开发了一种有效的口服疫苗载体，该载体由涂有M细胞靶向肽的聚乳酸-乙醇酸共聚物（PLGA）微粒组成。本研究以猪痢疾短螺旋体膜蛋白B（Bmp B）为模型疫苗，将其负载于多孔PLGA微球中。将PLGA MP进一步用与M细胞归巢肽（CKS 9）缀合的水溶性壳聚糖（WSC）包被以制备BmpB-CKS 9-WSC-PLGA MP。在小鼠中用CKS 9-WSC-PLGA MP口服免疫BmpB疫苗显示粘膜组织中分泌性伊加应答和全身性IgG抗体应答升高，提供完全的免疫应答。具体地，基于升高的IgG 1和IgG 2a滴度，用这些MP免疫证明诱导Th 1型和Th 2型应答。升高的免疫应答归因于CKS 9-WSC-PLGA MP对派尔集合淋巴结区域的增强的M细胞靶向和转胞吞能力。通过闭合回肠环测定研究了CKS 9-WSC-PLGA MP与M细胞进入小鼠小肠Peyer集结区的高结合亲和力，并通过共聚焦激光扫描显微镜进一步证实。这些结果表明，本研究中使用的M细胞靶向方法是一种有前途的靶向口服疫苗递送工具。(c)2013爱思唯尔有限公司保留所有权利。
M cells, the key players of the mucosal immunity induction, are one of the intestinal barriers for the efficient delivery of vaccines to mucosal immune tissues. To overcome the barrier, we have developed an efficient oral vaccine carrier that constitutes poly (lactic-co-glycolic acid) (PLGA) microparticle coated with M cell targeting peptide. In this study, a membrane protein B of Brachyspira hyodysenteriae (BmpB) as a model vaccine against swine dysentery was loaded into porous PLGA microparticles (MPs). The PLGA MPs were further coated with the water-soluble chitosan (WSC) conjugated with M cell homing peptide (CKS9) to prepare BmpB-CKS9-WSC-PLGA MPs. Oral immunization of BmpB vaccine with CKS9-WSC-PLGA MPs in mice showed elevated secretory IgA responses in the mucosa] tissues and systemic IgG antibody responses, providing a complete immune response. Specifically, the immunization with these MPs demonstrated to induce both Th1- and Th2-type responses based on elevated IgG1 and IgG2a titers. The elevated immune responses were attributed to the enhanced M cell targeting and transcytosis ability of CKS9-WSC-PLGA MPs to Peyer's patch regions. The high binding affinity of CKS9-WSC-PLGA MPs with the M cells to enter into the Peyer's patch regions of mouse small intestine was investigated by closed ileal loop assay and it was further confirmed by confocal laser scanning microscopy. These results suggest that the M cell targeting approach used in this study is a promising tool for targeted oral vaccine delivery. (c) 2013 Elsevier Ltd. All rights reserved.