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Expression of vFLIP in a lentiviral vaccine vector activates NF-{kappa}B, matures dendritic cells, and increases CD8+ T-cell responses

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Published copy (DOI)


  • Helen M Rowe
  • Luciene Lopes
  • Najmeeyah Brown
  • Sofia Efklidou
  • Timothy Smallie
  • Sarah Karrar
  • Paul M Kaye
  • Mary K Collins


Publication details

DatePublished - Feb 2009
Issue number4
Number of pages8
Pages (from-to)1555-62
Original languageEnglish


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-kappaB, vFLIP from Kaposi's sarcoma-associated herpesvirus (KSHV), in a lentivector to mature DCs. vFLIP activated NF-kappaB 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-kappaB activation is sufficient to induce many aspects of DC maturation and that expression of a constitutive NF-kappaB activator can improve the efficacy of a vaccine vector.

    Research areas

  • Animals, CD8-Positive T-Lymphocytes, Cancer Vaccines, Cytokines, Dendritic Cells, Leishmania donovani, Leishmaniasis, Lentivirus, Mice, NF-kappa B, Neoplasms, Ovalbumin, Receptors, Immunologic, Spleen, Survival Analysis, Viral Proteins, Viral Vaccines

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