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Augmentation of antigen-specific immune responses using DNA-fusogenic liposome vaccine
Authors:Yoshikawa Tomoaki  Imazu Susumu  Gao Jian-Qing  Hayashi Kazuyuki  Tsuda Yasuhiro  Shimokawa Mariko  Sugita Toshiki  Niwa Takako  Oda Atushi  Akashi Mitsuru  Tsutsumi Yasuo  Mayumi Tadanori  Nakagawa Shinsaku
Institution:Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Osaka University, Japan.
Abstract: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.
Keywords:DNA vaccine  Tumor vaccine  Liposome  Drug delivery system
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