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Targeting Dendritic Cells to Enhance DNA Vaccine Potency¹

Center for Cell and Gene Therapy [Z.Y., X.H., J.H., H.C.T., S-Y.C.], Departments of Molecular and Human Genetics [Z.Y., J.H., S-Y.C.], and Pediatrics [X.H., H.C.T.], Baylor College of Medicine, Houston, Texas 77030

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 responses by DNA vaccination. However, a major problem of DNA vaccination is its limited potency, because only a very limited fraction of injected DNA molecules are taken up by DCs. In this study, we describe a novel DNA vaccination strategy to enhance uptake and presentation of antigens by DCs. Specifically, we developed a DNA vaccine based upon expression of a model hepatitis B virus (HBV) e antigen fused to an IgG Fc fragment. After vaccination, the DNA are taken up by cells that produce and secrete the antigen-Fc fusion proteins. The secreted fusion proteins, in addition to inducing B cells, are efficiently captured and processed by DCs via receptor-mediated endocytosis and then presented to the MHC class II and as -I (cross-priming). The results of this study demonstrate that broad enhancement of antigen-specific CD4+ helper, CD8+ cytotoxic T-cell, and B-cell responses can be achieved by this DNA vaccination strategy. Thus, the strategy capable of inducing all arms of the adaptive immunity may provide a novel, generic design for the development of therapeutic and preventive DNA vaccines.

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