Augmentation of antigen-specific immune responses using DNA-fusogenic liposome vaccine.
In an attempt to enhance the immunological efficacy of genetic immunization, we investigated a new biological means for delivering antigen gene directly to the cytoplasm via membrane fusion. In this context, we investigated fusogenic liposome (FL) encapsulating DNA as a possible genetic immunization vehicle. RT-PCR analysis indicated that a FL could introduce and express encapsulating OVA gene efficiently and rapidly in vitro. Consistent with this observation, an in vitro assay showed that FL-mediated antigen-gene delivery can induce potent presentation of antigen via the MHC class I-dependent pathway. Accordingly, immunization with FL containing the OVA-gene induced potent OVA-specific Th1 and Th2 cytokine production. Additionally, OVA-specific CTL responses and antibody production were also observed in systemic compartments including the spleen, upon immunization with the OVA-gene encapsulating FL. These findings suggest that FL is an effective genetic immunization carrier system for the stimulation of antigen-specific immune responses against its encoding antigen.
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
Shimokawa
Mariko
M
Sugita
Toshiki
T
Niwa
Takako
T
Oda
Atushi
A
Akashi
Mitsuru
M
Tsutsumi
Yasuo
Y
Mayumi
Tadanori
T
Nakagawa
Shinsaku
S
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000941:Antigens / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D045744:Cell Line, Tumor; D004247:DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D005822:Genetic Vectors / Q000008:administration & dosage / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D007074:Immunoglobulin G / Q000235:genetics / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D008081:Liposomes; D008297:Male; D008561:Membrane Fusion / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D010714:Phosphatidylethanolamines / Q000276:immunology; D013154:Spleen / Q000166:cytology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
D000941:Antigens; D015395:Histocompatibility Antigens Class I; D007074:Immunoglobulin G; D008081:Liposomes; D010714:Phosphatidylethanolamines; D019444:Vaccines, DNA; D015847:Interleukin-4; C020888:1,2-dielaidoylphosphatidylethanolamine; D007371:Interferon-gamma; D010047:Ovalbumin; D004247:DNA