Development of plasmid DNA delivery methods to antigen presenting cells for optimized DNA vaccination

开发质粒 DNA 递送至抗原呈递细胞的方法，以优化 DNA 疫苗接种

• 批准号: 13470514
• 负责人: TAKAKURA Yoshinobu
• 金额: $ 7.04万
• 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: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13470514/
• 关键词: DNA vaccine; plasmid DNA; macrophage; dendritic cell; cationic carrier; local administration; antibody production; カチオン性高分子; 抗原提示細胞; 細胞取り込み; サイトカイン; CpGモチーフ

To construct a strategy for optimizing plasmid DNA delivery for DNA vaccination, a series of in vitro and in vivo studies were carried out. In vitro studies using cultured macrophages and dendritic cells demonstrated that a specific mechanism for polyanions would be involved in these cells. In vitro cellular activation experiments revealed that dendritic cells were activated by naked plasmid DNA and its cationic liposome complexes in CpG motif-dependent manner. On the other hand, macrophage activation by naked DNA was dependent on CpG motif while DNA can stimulate macrophages in a CpG motif-independent manner when it is complexed with the cationic liposomes. In vivo local immunization studies using mice demonstrated that plasmid DNA complexed with a cationic carrier, methylated bovine serum albumin can enhance antibody induction with DNA vaccination, suggesting that immune reactions can be modulated by the control of local disposition of plasmid DNA with complexation with the carrier, Thus, the present study provides useful in vitro and in vivo information about the DNA vaccination approach.

为了构建一种优化DNA疫苗载体DNA传递的策略，进行了一系列的体外和体内研究。用培养的巨噬细胞和树突状细胞进行的体外研究表明，这些细胞中涉及聚阴离子的特定机制。体外细胞活化实验表明，裸质粒DNA及其阳离子脂质体复合体以CpG基序依赖的方式激活树突状细胞。另一方面，裸露DNA对巨噬细胞的激活依赖于CpG基序，而DNA与阳离子脂质体复合后可以不依赖CpG基序的方式激活巨噬细胞。在小鼠体内的局部免疫研究表明，DNA与阳离子载体甲基化牛血清白蛋白复合后可增强DNA疫苗的抗体诱导作用，提示可通过控制DNA与载体的络合作用来调节免疫反应，从而为DNA疫苗的体外和体内研究提供了有用的信息。

项目成果

Takahara Yoshinaga et al.: "Efficient uptake and rapid degradation of plasmid DNA by murine dendritic cells via a specific mechanism"Biochemical and Biophysical Research Communications. 299(3). 389-394 (2002)

Takahara Yoshinaga 等人：“鼠树突状细胞通过特定机制有效摄取和快速降解质粒 DNA”生物化学和生物物理研究通讯。

Takaharu Yoshinaga et al.: "Efficient uptake and rapid degradation of plasmid DNA by murine dendritic cells via a specific mechanism"Biochemical Biophysical Research Communications. 299(3). 389-394 (2002)

Takaharu Yoshinaga 等人：“鼠树突状细胞通过特定机制有效摄取和快速降解质粒 DNA”《生物化学生物物理研究通讯》。

Kei Yasuda et al.: "Macrophages to Induce Inflammatory Cytokines in a CpG Motif-Independent Manner by Complex Formation with Cationic Liposomes"Biochemical Biophysical Research Communications. 293(1). 344-348 (2002)

Kei Yasuda 等人：“巨噬细胞通过与阳离子脂质体形成复合物，以 CpG 基序独立的方式诱导炎症细胞因子”生物化学生物物理研究通讯。

Takaharu Yoshinaga et al.: "Efficient uptake and rapid degradation of plasmid DNA by murine dendritic cells via a specific mechanism"Biochemical Biophysical Research Communications. 299(3). 389-384 (2002)

Takaharu Yoshinaga 等人：“鼠树突状细胞通过特定机制有效摄取和快速降解质粒 DNA”《生物化学生物物理研究通讯》。

Kei Yasuda et al.: "Plasmid DNA activates murine macrophages to induce inflammatory cytokines in a CpG motif-independent manner by complex formation with cationic liposomes"Biochemical Biophysical Research Communications. 293(1). 344-348 (2002)

Kei Yasuda 等人：“质粒 DNA 通过与阳离子脂质体形成复合物，以 CpG 基序独立的方式激活小鼠巨噬细胞，诱导炎症细胞因子”《生物化学生物物理研究通讯》。