Establishment of novel delivery strategies to dendritic cells and optimization of DNA vaccination

树突状细胞新型递送策略的建立和 DNA 疫苗接种的优化

• 批准号: 15390048
• 负责人: TAKAKURA Yoshinobu
• 金额: $ 9.34万
• 依托单位: Kyoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15390048/
• 关键词: DNA vaccination; Dendritic cell; Plasmid DNA; Delivery; Cytotoxic T cell; Intracellular trafficking; Electroporation; Intradermal injection; DNAキャリアー; 局所投与; 抗原提示細胞; 抗体産生; 免疫応答

DNA vaccination, which can induce humoral immunity as well as cellular immunity, is a promising approach for treatment of various infectious diseases and tumors. However, its optimization is required to improve the efficacy of this strategy. In particular, delivery to the dendritic cells is one of the most important factors since they play a main role in induction immunity following DNA vaccination. The purpose of this project was to establish the efficient delivery methods to dendritic cells which can optimize the therapeutic effect of DNA vaccine. We found that complex formation between plasmid DNA and cationic macromolecules could enhance antigen specific immune responses by DNA vaccination with intradermal injection. Furthermore, we developed novel plasmid vectors which can control the intracellular trafficking of antigen expressed. We found that intradermal injection of the vector in combination with electroporation could effectively induce antigen specific cytotoxic T cells. These findings would be useful for optimization of DNA vaccination approach.

DNA疫苗接种可以诱导体液免疫和细胞免疫，是治疗各种感染性疾病和肿瘤的一种很有前途的方法。然而，为了提高该策略的有效性，需要对其进行优化。特别是，递送到树突状细胞是最重要的因素之一，因为它们在DNA疫苗接种后的诱导免疫中起主要作用。本课题旨在建立有效的树突状细胞递送方法，以优化DNA疫苗的治疗效果。我们发现质粒DNA与阳离子大分子之间形成复合物可以通过皮内注射DNA疫苗增强抗原特异性免疫反应。此外，我们还开发了一种新的质粒载体，可以控制表达的抗原在细胞内的运输。我们发现皮内注射载体结合电穿孔可有效诱导抗原特异性细胞毒性T细胞。这些发现将有助于DNA疫苗接种方法的优化。

项目成果

Manipulation of local disposition and gene expression characteristics of plasmid DNA following intramuscular administration by complexation with cationic macromolecule

• DOI: 10.1016/j.ijpharm.2004.12.011
• 发表时间: 2005-04-11
• 期刊: INTERNATIONAL JOURNAL OF PHARMACEUTICS
• 影响因子: 5.8
• 作者: Kawase, A;Kobayashi, N;Takakura, Y
• 通讯作者: Takakura, Y