This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Rowe, H. M. Articles by Collins, M. K. Search for Related Content PubMed PubMed Citation Articles by Rowe, H. M. Articles by Collins, M. K.

 Previous Article  |  Next Article 

Journal of Virology, February 2009, p. 1555-1562, Vol. 83, No. 4
0022-538X/09/$08.00+0     doi:10.1128/JVI.00709-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Expression of vFLIP in a Lentiviral Vaccine Vector Activates NF-B, Matures Dendritic Cells, and Increases CD8⁺ T-Cell Responses

Helen M. Rowe,¹ Luciene Lopes,¹ Najmeeyah Brown,² Sofia Efklidou,¹ Timothy Smallie,³ Sarah Karrar,¹ Paul M. Kaye,² and Mary K. Collins^1*

MRC Centre for Medical Molecular Virology, Division of Infection and Immunity, University College London, Windeyer Building, 46 Cleveland St., London W1T 4JF, United Kingdom,¹ The Kennedy Institute of Rheumatology Division, ARC Building, Charing Cross Campus, Imperial College London, 1 Aspenlea Road, London W6 8LH, United Kingdom,³ Centre for Immunology and Infection, Department of Biology and Hull York Medical School, University of York, Wentworth Way, York YO10 5YW, United Kingdom²

Received 31 March 2008/ Accepted 14 November 2008

Lentiviral vectors deliver antigens to dendritic cells (DCs) in vivo, but they do not trigger DC maturation. We therefore expressed a viral protein that constitutively activates NF-B, vFLIP from Kaposi's sarcoma-associated herpesvirus (KSHV), in a lentivector to mature DCs. vFLIP activated NF-B in mouse bone marrow-derived DCs in vitro and matured these DCs to a similar extent as lipopolysaccharide; costimulatory markers CD80, CD86, CD40, and ICAM-1 were upregulated and tumor necrosis factor alpha and interleukin-12 secreted. The vFLIP-expressing lentivector also matured DCs in vivo. When we coexpressed vFLIP in a lentivector with ovalbumin (Ova), we found an increased immune response to Ova; up to 10 times more Ova-specific CD8⁺ T cells secreting gamma interferon were detected in the spleens of vFLIP_Ova-immunized mice than in the spleens of mice immunized with GFP_Ova. Furthermore, this increased CD8⁺ T-cell response correlated with improved tumor-free survival in a tumor therapy model. A single immunization with vFLIP_Ova also reduced the parasite load when mice were challenged with OVA-Leishmania donovani. In conclusion, vFLIP from KSHV is a DC activator, maturing DCs in vitro and in vivo. This demonstrates that NF-B activation is sufficient to induce many aspects of DC maturation and that expression of a constitutive NF-B activator can improve the efficacy of a vaccine vector.

---

* Corresponding author. Mailing address: MRC Centre for Medical Molecular Virology, Division of Infection and Immunity, University College London, Windeyer Building, 46 Cleveland St., London W1T 4JF, United Kingdom. Phone and fax: 44-207-6799301. E-mail: mary.collins{at}ucl.ac.uk

Published ahead of print on 26 November 2008.

---

Journal of Virology, February 2009, p. 1555-1562, Vol. 83, No. 4
0022-538X/09/$08.00+0     doi:10.1128/JVI.00709-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

This article has been cited by other articles:

• Karwacz, K., Mukherjee, S., Apolonia, L., Blundell, M. P., Bouma, G., Escors, D., Collins, M. K., Thrasher, A. J. (2009). Nonintegrating Lentivector Vaccines Stimulate Prolonged T-Cell and Antibody Responses and Are Effective in Tumor Therapy. J. Virol. 83: 3094-3103 [Abstract] [Full Text]