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Immunization with a Lentivector That Targets Tumor Antigen Expression to Dendritic Cells Induces Potent CD8⁺ and CD4⁺ T-Cell Responses

Luciene Lopes,¹ Marie Dewannieux,¹ Uzi Gileadi,² Ranbir Bailey,¹ Yasuhiro Ikeda,^1, Christopher Whittaker,¹ Matthew P. Collin,³ Vincenzo Cerundolo,² Mizuki Tomihari,⁴ Kiyoshi Ariizumi,⁴ and Mary K. Collins^1*

Division of Infection and Immunity, University College London, Windeyer Building, 46 Cleveland Street, London W1T 4JF, United Kingdom,¹ Tumour Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom,² Haematological Sciences, School of Clinical and Laboratory Sciences, University of Newcastle upon Tyne, Newcastle upon Tyne, United Kingdom,³ Department of Dermatology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas⁴

Received 13 June 2007/ Accepted 11 September 2007

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.

Published ahead of print on 24 October 2007.

Present address: Molecular Medicine Program, Mayo Clinic College of Medicine, Rochester, MN.

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