Expression of vFLIP in a Lentiviral Vaccine Vector Activates NF-κB, Matures Dendritic Cells, and Increases CD8+ T-Cell Responses▿
| Autor: | Luciene Lopes, Sarah Karrar, Helen M. Rowe, Sofia Efklidou, Mary Collins, Timothy Smallie, Najmeeyah Brown, Paul M. Kaye |
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| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
Ovalbumin
Immunology Antigen presentation chemical and pharmacologic phenomena CD8-Positive T-Lymphocytes Microbiology Cancer Vaccines Mice Viral Proteins Interferon Virology Neoplasms Vaccines and Antiviral Agents medicine Cytotoxic T cell Animals Receptors Immunologic Leishmaniasis CD86 CD40 biology Lentivirus NF-kappa B Viral Vaccines Dendritic cell Dendritic Cells Survival Analysis Insect Science biology.protein Cancer research Interleukin 12 Cytokines CD80 Spleen medicine.drug Leishmania donovani |
| Popis: | 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-κB, vFLIP from Kaposi's sarcoma-associated herpesvirus (KSHV), in a lentivector to mature DCs. vFLIP activated NF-κB 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-κB activation is sufficient to induce many aspects of DC maturation and that expression of a constitutive NF-κB activator can improve the efficacy of a vaccine vector. |
| Databáze: | OpenAIRE |
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