Targeting dendritic cells to enhance DNA vaccine potency

Z You, X Huang, J Hester, HC Toh, SY Chen - Cancer research, 2001 - AACR
Z You, X Huang, J Hester, HC Toh, SY Chen
Cancer research, 2001AACR
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 …
Abstract
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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