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Journal of Virology, April 2009, p. 3094-3103, Vol. 83, No. 7
0022-538X/09/$08.00+0     doi:10.1128/JVI.02519-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Nonintegrating Lentivector Vaccines Stimulate Prolonged T-Cell and Antibody Responses and Are Effective in Tumor Therapy{triangledown}

Katarzyna Karwacz,2,{dagger} Sayandip Mukherjee,1,{dagger} Luis Apolonia,1 Michael P. Blundell,1 Gerben Bouma,1 David Escors,2 Mary K. Collins,2,{ddagger}* and Adrian J. Thrasher1,{ddagger}

UCL, Institute of Child Health, Centre for Immunodeficiency, Molecular Immunology Unit, 30 Guilford Street, London, United Kingdom,1 Division of Infection and Immunity, University College London, London, United Kingdom2

Received 8 December 2008/ Accepted 20 January 2009

Lentiviral vectors (lentivectors) are effective for stimulation of cell-mediated and humoral immunity following subcutaneous and intramuscular immunization. However, lentivector genome integration carries a risk of perturbation of host gene expression. Here, we demonstrate that lentivectors with multiple mutations that prevent integration are also effective immunogens. First, systemic CD8+ T-cell responses to the model antigen ovalbumin were detected following subcutaneous injection of nonintegrating lentivectors. Transfer of transgenic OT1 T cells demonstrated that antigen presentation persisted for at least 30 days. Furthermore, an enhanced CD8+ T-cell response, peaking at 7 days, was stimulated by coexpression of p38 MAP kinase or an NF-{kappa}B activator from the same vector. Second, we demonstrated systemic CD8+ T-cell and antibody responses to the secreted hepatitis B virus (HBV) surface antigen expressed from a nonintegrating lentivector injected intramuscularly. The induction, specificity, and kinetics of antibody production closely mimicked those of natural HBV infection. In this case, both the vector genome and the immune response were maintained for at least 2 months. Together, our data indicate that nonintegrating lentivectors can be employed to generate effective vaccines.

* Corresponding author. Mailing address: Infection and Immunity, Windeyer Building, 46 Cleveland St., London W1T 4JF, United Kingdom. Phone and fax: 44-2076799301. E-mail: mary.collins{at}ucl.ac.uk

{triangledown} Published ahead of print on 28 January 2009.

{dagger} These authors contributed equally to the study.

{ddagger} These authors contributed equally to the study.

Journal of Virology, April 2009, p. 3094-3103, Vol. 83, No. 7
0022-538X/09/$08.00+0     doi:10.1128/JVI.02519-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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