title: Non-methylated CpG motif packaged into fusogenic liposomes enhance antigen-specific immunity in mice.
abstract: 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.
authors.affiliation: Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Osaka University, Japan.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Yoshikawa
authors.forename: Susumu
authors.initials: S
authors.lastname: Imazu
authors.forename: Jian-Qing
authors.initials: JQ
authors.lastname: Gao
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Hayashi
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Tsuda
authors.forename: Naoki
authors.initials: N
authors.lastname: Okada
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Tsutsumi
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Akashi
authors.forename: Tadanori
authors.initials: T
authors.lastname: Mayumi
authors.forename: Shinsaku
authors.initials: S
authors.lastname: Nakagawa
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology*; D049109:Cell Proliferation / Q000187:drug effects; D018899:CpG Islands / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D007109:Immunity / Q000276:immunology*; D018664:Interleukin-12 / Q000096:biosynthesis; D008081:Liposomes; D008297:Male; D008745:Methylation; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D010957:Plasmids / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology; D014611:Vaccination; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000276:immunology*
chemical_list: D000941:Antigens; D008081:Liposomes; D019444:Vaccines, DNA; D018664:Interleukin-12; D010047:Ovalbumin