Abstract
We report a method of inducing antigen production in dendritic cells by in vivo targeting with lentiviral vectors that specifically bind to the dendritic cell-surface protein DC-SIGN. To target dendritic cells, we enveloped the lentivector with a viral glycoprotein from Sindbis virus engineered to be DC-SIGN-specific. In vitro, this lentivector specifically transduced dendritic cells and induced dendritic cell maturation. A high frequency (up to 12%) of ovalbumin (OVA)-specific CD8(+) T cells and a significant antibody response were observed 2 weeks after injection of a targeted lentiviral vector encoding an OVA transgene into naive mice. This approach also protected against the growth of OVA-expressing E.G7 tumors and induced regression of established tumors. Thus, lentiviral vectors targeting dendritic cells provide a simple method of producing effective immunity and may provide an alternative route for immunization with protein antigens.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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B-Lymphocytes / cytology
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B-Lymphocytes / immunology
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CD8-Positive T-Lymphocytes / cytology
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CD8-Positive T-Lymphocytes / immunology
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Cancer Vaccines / immunology*
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Cell Adhesion Molecules / metabolism
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Cell Line
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Dendritic Cells / cytology
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Dendritic Cells / immunology*
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Dendritic Cells / metabolism*
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Female
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Gene Expression
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Genetic Vectors / genetics*
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Humans
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Lectins, C-Type / metabolism
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Lentivirus / genetics*
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Neoplasms, Experimental / immunology
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Neoplasms, Experimental / therapy
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Ovalbumin / genetics
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Ovalbumin / immunology
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Receptors, Cell Surface / metabolism
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Sensitivity and Specificity
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Sindbis Virus / genetics
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Sindbis Virus / metabolism
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Transduction, Genetic
Substances
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Cancer Vaccines
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Cell Adhesion Molecules
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DC-specific ICAM-3 grabbing nonintegrin
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Lectins, C-Type
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Receptors, Cell Surface
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Ovalbumin