Immunostimulatory effect of IL-18-encoding plasmid in DNA vaccination against murine Schistosoma mansoni infection
Immunostimulatory effect of IL-18-encoding plasmid in DNA vaccination against murine Schistosoma mansoni infection
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DOI：
10.1016/s0264-410x(00)00363-7
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发表时间：
2001-01-08
期刊：
影响因子：
5.5
通讯作者：
Locht, C
中科院分区：
文献类型：
--
作者：
Dupré, L;Kremer, L;Locht, C
在体内传递编码抗原的DNA是诱导对病原体的免疫反应的一种简单工具。这种疫苗接种方法还提供了共传递编码免疫调节分子的质粒的可能性，以驱动免疫反应达到最佳保护效果。在曼氏血吸虫感染的小鼠模型中，疫苗接种诱导Th1谱已被证明具有保护作用。在这项研究中，我们使用了一种编码th1促进细胞因子IL-18的质粒，因为我们观察到Balb/c小鼠经皮感染强烈诱导皮肤中IL-18 mRNA的产生。在感染前皮内注射il -18编码质粒不会干扰寄生虫通过皮肤的迁移，尽管它会导致局部和短暂的细胞浸润。当il -18编码质粒与Sm28GST编码质粒共递送时，脾脏细胞分泌抗原特异性ifn - γ的量比仅接受Sm28GST编码质粒的小鼠脾脏细胞增加了30倍。这种免疫刺激作用与显著的保护作用（产卵减少28%，虫负荷减少23%）有关，这归因于两种质粒之间的协同作用。因此，本研究表明，il -18编码质粒与抗原编码质粒共递送可刺激特异性细胞反应，并诱导对曼氏链球菌感染的保护作用。2001爱思唯尔科学有限公司版权所有。
In vivo delivery of DNA encoding antigens is a simple tool to induce immune responses against pathogens. This approach to vaccination also offers the possibility to codeliver plasmids encoding immunomodulatory molecules in order to drive immune responses towards optimal protective effects. In the murine model of Schistosoma mansoni infection, vaccination inducing a Th1 profile has been shown to be protective. In this study, we used a plasmid encoding the Th1-promoting cytokine IL-18, since we observed that percutaneous infection of Balb/c mice strongly induced the production of IL-18 mRNA in the skin. Intradermal injection of the IL-18-encoding plasmid prior to infection did not interfere with parasite migration through the skin although it led to a local and transient cellular infiltration. When the IL-18-encoding plasmid was codelivered with a S. mansoni glutathione S-transferase (Sm28GST)-encoding plasmid, a 30-fold increase of antigen-specific IFN-gamma secretion by spleen cells was observed in comparison to spleen cells from mice that had received only the Sm28GST-encoding plasmid. This immunostimulatory effect was related to a significant protective effect (28% reduction in egg laying and 23% reduction in worm burden) which was attributed to a cooperative effect between both plasmids. Therefore, this study shows that codelivery of an IL-18-encoding plasmid with an antigen-encoding plasmid can stimulate specific cellular responses and induce protective effects against S. mansoni infection. (C) 2001 Elsevier Science Ltd. All rights reserved.