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Immunization with a lentivector that targets tumor antigen expression to dendritic cells induces potent CD8+ and CD4+ T-cell responses

Lookup NU author(s): Professor Matthew CollinORCiD

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Abstract

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-Ab. 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. Copyright © 2008, American Society for Microbiology. All Rights Reserved.


Publication metadata

Author(s): Lopes L, Dewannieux M, Gileadi U, Bailey R, Ikeda Y, Whittaker C, Collin MP, Cerundolo V, Tomihari M, Ariizumi K, Collins MK

Publication type: Article

Publication status: Published

Journal: Journal of Virology

Year: 2008

Volume: 82

Issue: 1

Pages: 86-95

ISSN (print): 0022-538X

ISSN (electronic): 1070-6321

Publisher: American Society for Microbiology

URL: http://dx.doi.org/10.1128/JVI.01289-07

DOI: 10.1128/JVI.01289-07

PubMed id: 17959670


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