Enhanced DNA vaccine potency by mannosytated lipoplex after intraperitoneal administration

Background Here we describe a novel DNA vaccine formulation that can enhance cytotoxic T lymphocyte (CTL) activity through efficient gene delivery to dendritic cells (DCs) by mannose receptor-mediated endocytosis. Methods Ovalbumin (OVA) was selected as a model antigen for vaccination; accordingly, OVA-encoding pDNA (pCMV-OVA) was constructed to evaluate DNA vaccination. Mannosylated cationic liposomes (Manliposomes) were prepared using cholesten-5-yloxy-N-{4-[(1-imino-2-D-thiomannosylethyl) amino]butyl}formamide (Man-C4-Chol) with cationic lipid. The potency of the mannosylated liposome/pCMV (Man-lipoplex) was evaluated by measuring OVA mRNA in CD11c(+) cells, CTL activity, and the OVA-specific anti-tumor effect after in vivo administration. Results An in vitro study using DC2.4 cells demonstrated that Manliposomes could transfect pCMV-OVA more efficiently than cationic liposomes via mannose receptor-mediated endocytosis. In vivo studies revealed that the Man-lipoplex exhibited higher OVA mRNA expression in CD11c+ cells in the spleen and peritoneal cavity and provided a stronger OVA-specific CTL response than intraperitoneal (i.p.) administration of the conventional lipoplex and intramuscular (i.m.) administration of naked pCMV-OVA, the standard protocol for DNA vaccination. Pre-immunization with the Man-lipoplex provided much better OVA-specific anti-tumor effect than naked pCMV-OVA via the i.m. route. Conclusions These results suggested that in vivo active targeting of DNA vaccine to DCs with Man-lipoplex might prove useful for the rational design of DNA vaccine. Copyright (c) 2006 John Wiley & Sons, Ltd.