Non-Methylated CpG Motif Packaged into Fusogenic Liposomes Enhance Antigen-Specific Immunity in Mice

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  • Yoshikawa Tomoaki
    Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Osaka University “Creation of bio-devices and bio-systems with chemical and biological molecules for medical use”, CREST, Japan Science and Technology Agency (JST)
  • Imazu Susumu
    Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Osaka University
  • Gao Jian-Qing
    Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Osaka University Department of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University
  • Hayashi Kazuyuki
    Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Osaka University
  • Tsuda Yasuhiro
    Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Osaka University
  • Okada Naoki
    Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Osaka University Department of Biopharmaceutics, Kyoto Pharmaceutical University
  • Tsutsumi Yasuo
    National Institute of Biomedical Innovation, Japan
  • Akashi Mitsuru
    “Creation of bio-devices and bio-systems with chemical and biological molecules for medical use”, CREST, Japan Science and Technology Agency (JST) Department of Molecular Chemistry, Graduate School of Engineering, Osaka University
  • Mayumi Tadanori
    Kobegakuin University
  • Nakagawa Shinsaku
    Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Osaka University “Creation of bio-devices and bio-systems with chemical and biological molecules for medical use”, CREST, Japan Science and Technology Agency (JST)

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DNA rich in non-methylated CG motifs (CpGs) enhances induction of immune responses against co-administered antigen encoding genes. CpGs are therefore among the promising adjuvants known to date. However, naked plasmid DNA, even which contains CpG motifs, are taken up by antigen presenting cells via the endocytosis pathway. Endocytosed DNAs are thus degraded and their gene expression levels are inefficient. In this context, an effective plasmid delivery carrier is required for DNA vaccine development. We show in the present study that packaging plasmids containing CpGs into fusogenic liposomes (FL) derived from conventional liposomes and Sendai virus-derived active accessory proteins is an attractive method for enhancing the efficacy of a DNA vaccine. These CpG-enhanced plasmids (possessing 16 CpG repeats) that were packaged into FL, enhanced ovalbumin (OVA)-specific T cell proliferation and cytotoxic T cell activity after immunization. In fact, vaccination with CpG enhanced plasmid-loaded FL induced effective prophylactic effects compared with 13 repeats CpG containing plasmid in a tumor challenge experiment. Thus, the development of a CpG-enhanced DNA-FL genetic immunization system represents a promising tool for developing candidate vaccines against some of the more difficult infectious, parasitic, and oncologic disease targets.

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