DNA immunization using a non-viral promoter.
Most DNA vaccines rely on strong viral promoters to optimize levels of transgene expression. Some studies have demonstrated that the potency of viral promoters does not necessarily correlate with DNA vaccine efficacy in vivo. This has partly been attributed to downregulation of these promoters by cytokines such as interferon gamma induced by the CpG motives of these vaccines. In an attempt to avoid downregulation of viral promoters by IFN-gamma, we tested vaccine vectors driven by the MHC class II promoter. To enhance the activity of this promoter, another plasmid expressing the human MHC class II transactivator driven by a viral promoter, the native IFN-gamma inducible CIITA type IV promoter (PIV) or a synthetic promoter containing IFN-gamma inducible elements was co-inoculated. Our data show that a non-viral promoter such as the MHC class II promoter tested in this study can indeed be used in DNA vaccines.
Vanniasinkam
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The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA.
Reddy
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Ertl
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HC
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects; D015683:Gene Products, gag / Q000235:genetics / Q000276:immunology; D005814:Genes, Viral / Q000235:genetics; D005822:Genetic Vectors / Q000235:genetics; D006023:Glycoproteins / Q000235:genetics / Q000276:immunology; D007371:Interferon-gamma / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D009687:Nuclear Proteins / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011820:Rabies virus / Q000235:genetics / Q000276:immunology; D015534:Trans-Activators / Q000235:genetics*; D014158:Transcription, Genetic; D019076:Transgenes / Q000235:genetics; D019444:Vaccines, DNA / Q000235:genetics* / Q000276:immunology*; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology; D014765:Viral Vaccines / Q000235:genetics / Q000276:immunology
D015683:Gene Products, gag; D006023:Glycoproteins; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D015534:Trans-Activators; D019444:Vaccines, DNA; D014764:Viral Proteins; D014765:Viral Vaccines; D007371:Interferon-gamma