Targeting dendritic cells to enhance DNA vaccine potency

DNA vaccination that can induce both cellular and humoral immune responses has become an attractive immunization strategy against cancer and infection . Dendritic cells (DCs) play a critical role in the induction of immune res ponses by DNA vaccination. However, a major problem of DNA vaccination is i ts limited potency, because only a very limited fraction of injected DNA mo lecules are taken up by DCs. In this study, we describe a novel DNA vaccina tion strategy to enhance uptake and presentation of antigens by DCs. Specif ically, we developed a DNA vaccine based upon expression of a model hepatit is B virus (HBV) e antigen fused to an Ige Fc fragment. After vaccination, the DNA are taken up hy cells that produce and secrete the antigen-Fc fusio n proteins. The secreted fusion proteins, in addition to inducing B cells, are efficiently captured and processed by DCs via receptor-mediated endocyt osis and then presented to the MHC class II and as -I (cross-priming). The results of this study demonstrate that broad enhancement of antigen-specifi c CD4+ helper, CD8+ cytotoxic T-cell, and B-cell responses can be achieved by this DNA vaccination strategy, Thus, the strategy capable of inducing al l arms of the adaptive immunity may provide a novel, generic design for the development of therapeutic and preventive DNA vaccines.