Non-methylated CpG motif packaged into fusogenic liposomes enhance antigen-specific immunity in mice.
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.
Yoshikawa
Tomoaki
T
Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Osaka University, Japan.
Imazu
Susumu
S
Gao
Jian-Qing
JQ
Hayashi
Kazuyuki
K
Tsuda
Yasuhiro
Y
Okada
Naoki
N
Tsutsumi
Yasuo
Y
Akashi
Mitsuru
M
Mayumi
Tadanori
T
Nakagawa
Shinsaku
S
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*
D000941:Antigens; D008081:Liposomes; D019444:Vaccines, DNA; D018664:Interleukin-12; D010047:Ovalbumin