Enhancement of immune responses by DNA vaccination through targeted gene delivery using mannosylated cationic liposome formulations following intravenous administration in mice.
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.
Hattori
Yoshiyuki
Y
Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
Kawakami
Shigeru
S
Suzuki
Sachiko
S
Yamashita
Fumiyoshi
F
Hashida
Mitsuru
M
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*
D039521:CD11c Antigen; D016207:Cytokines; D008081:Liposomes; D019444:Vaccines, DNA; D007371:Interferon-gamma; D010047:Ovalbumin; D008358:Mannose