Jiang Hu-Lin, Kang Mi Lan, Quan Ji-Shan, Kang Sang Gyun, Akaike Toshihiro, Yoo Han Sang, Cho Chong-Su
Department of Agricultural Biotechnology, Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul, Republic of Korea.
Biomaterials. 2008 Apr;29(12):1931-9. doi: 10.1016/j.biomaterials.2007.12.025. Epub 2008 Jan 25.
A vaccine delivery system based on mannosylated chitosan microspheres (MCMs) was studied in vitro and in vivo. Bordetella bronchiseptica antigens containing dermonecrotoxin (BBD) were loaded in MCMs or chitosan microspheres (CMs). Fluorescence confocal microscopy indicated that BBD-loaded MCMs (BBD-MCMs) bound with mannose receptors on murine macrophages (RAW264.7 cells). In vitro experiments using macrophages demonstrated that BBD-MCMs had more effective immune-stimulating activity than BBD-loaded CMs (BBD-CMs). Mice intranasally immunized with BBD-MCMs showed significantly higher BBD-specific IgA antibody responses in saliva and serum than mice immunized with BBD-CMs (p<0.05). After challenge with B. bronchiseptica via the nasal cavity, groups treated with BBD-MCMs or BBD-CMs showed similar patterns with a high survival rate even though there was no significant difference between those groups. These results suggested that mannose moieties in the MCMs enhanced immune-stimulating activities through mucosal delivery due to a specific interaction between mannose groups in the MCMs and mannose receptors on the macrophages.
对基于甘露糖基化壳聚糖微球(MCMs)的疫苗递送系统进行了体外和体内研究。将含有皮肤坏死毒素(BBD)的支气管败血波氏杆菌抗原负载于MCMs或壳聚糖微球(CMs)中。荧光共聚焦显微镜显示,负载BBD的MCMs(BBD-MCMs)与小鼠巨噬细胞(RAW264.7细胞)上的甘露糖受体结合。使用巨噬细胞进行的体外实验表明,BBD-MCMs比负载BBD的CMs(BBD-CMs)具有更有效的免疫刺激活性。经鼻内免疫BBD-MCMs的小鼠在唾液和血清中显示出比免疫BBD-CMs的小鼠显著更高的BBD特异性IgA抗体反应(p<0.05)。经鼻腔用支气管败血波氏杆菌攻击后,用BBD-MCMs或BBD-CMs处理的组显示出相似的模式,即使这些组之间没有显著差异,但存活率很高。这些结果表明,MCMs中的甘露糖部分通过粘膜递送增强了免疫刺激活性,这是由于MCMs中的甘露糖基团与巨噬细胞上的甘露糖受体之间的特异性相互作用。