Development of plasmid DNA delivery methods to antigen presenting cells for optimized DNA vaccination

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To construct a strategy for optimizing plasmid DNA delivery for DNA vaccination, a series of in vitro and in vivo studies were carried out. In vitro studies using cultured macrophages and dendritic cells demonstrated that a specific mechanism for polyanions would be involved in these cells. In vitro cellular activation experiments revealed that dendritic cells were activated by naked plasmid DNA and its cationic liposome complexes in CpG motif-dependent manner. On the other hand, macrophage activation by naked DNA was dependent on CpG motif while DNA can stimulate macrophages in a CpG motif-independent manner when it is complexed with the cationic liposomes. In vivo local immunization studies using mice demonstrated that plasmid DNA complexed with a cationic carrier, methylated bovine serum albumin can enhance antibody induction with DNA vaccination, suggesting that immune reactions can be modulated by the control of local disposition of plasmid DNA with complexation with the carrier, Thus, the present study provides useful in vitro and in vivo information about the DNA vaccination approach.