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J. Virol. doi:10.1128/JVI.01289-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Immunisation with a lentivector that targets tumour antigen expression to dendritic cells induces potent CD8+ and CD4 + T cell responses

Division of Infection and Immunity, University College London, Windeyer Building, 46 Cleveland St, London W1T 4JF, UK; Tumour Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, UK; Haematological Sciences, School of Clinical & Laboratory Sciences, University of Newcastle upon Tyne, UK; Department of Dermatology, UT Southwestern Medical Center at Dallas, Dallas, Texas, USA

^* To whom correspondence should be addressed. Email: mary.collins{at}ucl.ac.uk.

	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 promoter. This lentivector expressed a 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 immunisation 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 DC can provide a safe and effective vaccine.

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• Escors, D., Lopes, L., Lin, R., Hiscott, J., Akira, S., Davis, R. J., Collins, M. K. (2008). Targeting dendritic cell signaling to regulate the response to immunization. Blood 111: 3050-3061 [Abstract] [Full Text]