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

DNA疫苗不仅能诱导细胞免疫，还能诱导体液免疫，是治疗各种感染性疾病和肿瘤的有效方法。然而，需要对其进行优化以提高该策略的功效。特别地，递送至树突状细胞是最重要的因素之一，因为它们在DNA疫苗接种后的诱导免疫中起主要作用。本课题的目的是建立一种有效的树突状细胞靶向方法，以优化DNA疫苗的治疗效果。我们发现，质粒DNA与阳离子大分子形成复合物可增强皮内注射DNA疫苗的抗原特异性免疫应答。此外，我们开发了新的质粒载体，可以控制细胞内运输的抗原表达。我们发现皮内注射载体结合电穿孔可以有效地诱导抗原特异性细胞毒性T细胞。这些结果将有助于DNA疫苗接种方法的优化。

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.