Abstract
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 (Man‐liposomes) 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‐OVA complex (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 Man‐liposomes 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 © 2006 John Wiley & Sons, Ltd.