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

• Project/Area Number: 13470514
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: 応用薬理学・医療系薬学
• Research Institution: KYOTO UNIVERSITY
• Principal Investigator: TAKAKURA Yoshinobu Kyoto University, Grad. Sch. Pharm. Sci., Professor, 薬学研究科, 教授 (30171432)
• Co-Investigator(Kenkyū-buntansha): YAMAOKA Kiyoshi Kyoto University, Grad. Sch. Pharm. Sci., Associate Professor, 薬学研究科, 助教授 (50109013)
• Project Period (FY): 2001 – 2002
• Project Status: Completed (Fiscal Year 2002)
• Budget Amount: ¥11,000,000 (Direct Cost: ¥11,000,000); Fiscal Year 2002: ¥3,500,000 (Direct Cost: ¥3,500,000); Fiscal Year 2001: ¥7,500,000 (Direct Cost: ¥7,500,000)
• Keywords: 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

Research Abstract

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.

Research Products

• [Publications] 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)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] 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)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] 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)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] 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)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] 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)
• [Publications] 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)