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A Combined Pox-virus/Lentiviral Vector System to Treat HIV Infection; Immunisation and Direct In Vivo Gene Transfer in T-Lymphocytes
Framework programme:
Project number:
EC contribution:
€ 1 180 000
36 months
Starting date:
1 December 2005

Keywords: HIV/AIDS; vaccine; gene therapy


HIV infection in humans induces chronic changes in the phenotype and function of CD4, CD8 and dendritic cells, which are only partly restored after the initiation of highly active anti-retroviral therapy (HAART). In order to alleviate the permanent dependency on HAART, alternative therapies, whose goal is to restore normal immune function, must be developed. Attenuated pox-viruses are currently under evaluation as prophylactic or therapeutic vaccines against AIDS. Development of a successful pox-virus vaccine is still a significant challenge due to the nature of HIV-1 infection, despite the fact that pox-virus vector vaccines can induce potent humoral and cellular immune responses, and have been developed for large-scale vaccine production under GMP conditions. This project will exploit this knowledge and employ state of the art bioengineering to create a pox-virus vector that encodes, in addition to specific HIV-1 proteins, a fully functional lentiviral vector genome delivering heterologous genes with HIV inhibitory capacity. Cells infected with modified vaccinia virus ankara (MVA) will simultaneously be converted into packaging cells capable of releasing transducing particles and cells expressing HIV-1 proteins for the stimulation of antigen specific cells. Consequently, the pox-gene vector will serve a dual role as a therapeutic vaccine and as in vivo gene therapy. The transducing particles released in vivo will protect naïve, memory and activated T-cells (including HIV antigen-specific T-cells) from HIV infection. During the course of this project, the pox-gene efficiency for transduction of T-cells in vitro and in vivo using marker genes will be demonstrated. Finally, after proof of concept has been achieved in mice, a small pilot study in SHIV infected macaques will be performed. This approach should elicit significant improvement in the management of HIV infection and reduce the costs involved by limiting dependency on HAART. Most importantly, the pox-gene vector has the potential for worldwide application, including use in developing countries.

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