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Content archived on 2024-06-25

A combined pox-virus/lentiviral vector system to treat HIV infection. Immunization and direct in vivo gene transfer in T lymphocytes.

Objective

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 HAART. In order to alleviate the permanent dependency on HAART, alternative therapies whos e goal is to restore normal immune functions 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 t o the nature of HIV-1 infection, despite the fact that pox-virus vector vaccines can induce potent immune response and have been developed for large scale vaccine production using GMP conditions. In this project, we shall exploit this knowledge and employ high level bioengineering to create a pox-virus vector that encodes, in addition to some HIV-1 proteins, a fully functional lentiviral vector genome delivering heterologous genes with HIV inhibitory capacity. Cells infected with Modified Vaccinia Ankara (M VA) 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 therapeuti c 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. Over the course of this project we shall demonstrate the Pox-Gen e efficiency for transduction of T cells in vitro and in vivo using marker genes. Finally after proof of concept has been obtained in mice we will perform a small pilot study in SHIV infected macaque. This approach should elicit significant improvement in the management of HIV infection and reduce the costs by limiting dependency on HAART. Most importantly, the Pox-Gene vector has the potential for world-wide application, including use in developing countries.

Fields of science (EuroSciVoc)

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Topic(s)

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Call for proposal

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FP6-2004-LIFESCIHEALTH-5
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Funding Scheme

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STREP - Specific Targeted Research Project

Coordinator

BIOMEDICAL PRIMATE RESEARCH CENTRE
EU contribution
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Total cost

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Participants (5)

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