title: Enhancement of immune responses by DNA vaccination through targeted gene delivery using mannosylated cationic liposome formulations following intravenous administration in mice.
abstract: The present study investigated the potency of the mannosylated cationic liposomes (Man liposomes) that we have developed in novel DNA vaccine carrier. Ovalbumin (OVA) was selected as a model antigen for vaccination; accordingly, OVA-encoding pDNA (pCMV-OVA) was constructed to evaluate DNA vaccination. The potency of the Man liposome/pCMV-OVA complex was compared with naked pCMV-OVA and that complexed with DC-Chol liposomes. In cultured mouse peritoneal macrophages, MHC class I-restricted antigen presentation of the Man liposome/pCMV-OVA complex was significantly higher than that of naked pCMV-OVA and that complexed with DC-Chol liposomes. After intravenous administration, OVA mRNA expression and MHC class I-restricted antigen presentation on CD11c+ cells and inflammatory cytokines, such as TNF-alpha, IL-12, and IFN-gamma, that can enhance the Th1 response of the Man liposome/pCMV-OVA complex were higher than that of naked pCMV-OVA and that complexed with DC-Chol liposomes. Also, the spleen cells from mice immunized by intravenous administration of the Man liposome/pCMV-OVA complex showed the highest proliferation response and IFN-gamma secretion. These findings suggest that the targeted delivery of DNA vaccine by Man liposomes is a potent vaccination method for DNA vaccine therapy.
authors.affiliation: Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Hattori
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kawakami
authors.forename: Sachiko
authors.initials: S
authors.lastname: Suzuki
authors.forename: Fumiyoshi
authors.initials: F
authors.lastname: Yamashita
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Hashida
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000276:immunology; D039521:CD11c Antigen / Q000276:immunology; D002645:Chickens; D016207:Cytokines / Q000096:biosynthesis; D003587:Cytomegalovirus / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D018014:Gene Transfer Techniques; D007371:Interferon-gamma / Q000378:metabolism; D008081:Liposomes / Q000008:administration & dosage* / Q000737:chemistry; D017737:Macrophages, Peritoneal / Q000276:immunology; D008358:Mannose / Q000008:administration & dosage* / Q000737:chemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D010047:Ovalbumin / Q000737:chemistry / Q000276:immunology; D010316:Particle Size; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*
chemical_list: D039521:CD11c Antigen; D016207:Cytokines; D008081:Liposomes; D019444:Vaccines, DNA; D007371:Interferon-gamma; D010047:Ovalbumin; D008358:Mannose