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Lentivectors stimulate potent immune responses to antigen transgenes and are being developed as novel genetic vaccines. To improve safety while retaining efficacy, we constructed a lentivector in which transgene expression was restricted to antigen-presenting cells using the mouse dectin-2 gene promoter. This lentivector expressed a green fluorescent protein (GFP) transgene in mouse bone marrow-derived dendritic cell cultures and in human skin-derived Langerhans and dermal dendritic cells. In mice GFP expression was detected in splenic dectin-2(+) cells after intravenous injection and in CD11c(+) dendritic cells in the draining lymph node after subcutaneous injection. A dectin-2 lentivector encoding the human melanoma antigen NY-ESO-1 primed an NY-ESO-1-specific CD8(+) T-cell response in HLA-A2 transgenic mice and stimulated a CD4(+) T-cell response to a newly identified NY-ESO-1 epitope presented by H2 I-A(b). As immunization with the optimal dose of the dectin-2 lentivector was similar to that stimulated by a lentivector containing a strong constitutive viral promoter, targeting antigen expression to dendritic cells can provide a safe and effective vaccine.

Original publication

DOI

10.1128/JVI.01289-07

Type

Journal article

Journal

J Virol

Publication Date

01/2008

Volume

82

Pages

86 - 95

Keywords

Animals, Antigens, Neoplasm, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Cells, Cultured, Dendritic Cells, Epitopes, Genes, Reporter, Genetic Vectors, Green Fluorescent Proteins, Humans, Lectins, C-Type, Lentivirus, Lymph Nodes, Membrane Proteins, Mice, Mice, Transgenic, Promoter Regions, Genetic, Spleen, Viral Vaccines