Abstract
Dendritic cells (DC) are the major APCs involved in naive T cell activation making them prime targets of vaccine research. We observed that mRNA was efficiently transfected, resulting in superior translation in DC compared with other professional APCs. A single stimulation of T cells by HIV gag-encoded mRNA-transfected DC in vitro resulted in primary CD4(+) and CD8(+) T cell immune responses at frequencies of Ag-specific cells (5-12.5%) similar to primary immune responses observed in vivo in murine models. Additionally, mRNA transfection also delivered a maturation signal to DC. Our results demonstrated that mRNA-mediated delivery of encoded Ag to DC induced potent primary T cell responses in vitro. mRNA transfection of DC, which mediated efficient delivery of antigenic peptides to MHC class I and II molecules, as well as delivering a maturation signal to DC, has the potential to be a potent and effective anti-HIV T cell-activating vaccine.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Antigen Presentation / genetics
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CD4-Positive T-Lymphocytes / immunology
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CD8-Positive T-Lymphocytes / immunology
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Cell Differentiation / genetics
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Cell Differentiation / immunology
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Cells, Cultured
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Cytotoxicity, Immunologic / genetics
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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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Dendritic Cells / virology
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Gene Products, gag / biosynthesis
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Gene Products, gag / genetics*
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Gene Products, gag / metabolism
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Genes, Reporter / immunology
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HIV / genetics*
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Histocompatibility Antigens Class I / metabolism*
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Histocompatibility Antigens Class II / metabolism*
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Humans
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Immunologic Memory / genetics
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RNA, Messenger / genetics*
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RNA, Messenger / pharmacology
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RNA, Viral / genetics
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T-Lymphocyte Subsets / immunology*
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T-Lymphocytes, Cytotoxic / immunology
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Transfection*
Substances
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Gene Products, gag
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Histocompatibility Antigens Class I
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Histocompatibility Antigens Class II
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RNA, Messenger
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RNA, Viral