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，是治疗各种传染病和肿瘤的一种有前途的方法。然而，需要对其进行优化以提高该策略的效率。特别是，递送至树突状细胞是最重要的因素之一，因为它们在 DNA 疫苗接种后诱导免疫中发挥主要作用。该项目的目的是建立树突状细胞的有效递送方法，以优化DNA疫苗的治疗效果。我们发现，通过皮内注射DNA疫苗接种，质粒DNA和阳离子大分子之间形成复合物可以增强抗原特异性免疫反应。此外，我们开发了新型质粒载体，可以控制表达的抗原的细胞内运输。我们发现皮内注射载体结合电穿孔可以有效诱导抗原特异性细胞毒性T细胞。这些发现将有助于优化 DNA 疫苗接种方法。

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