Community Research and Development Information Service - CORDIS

FP6

POX-GENE Report Summary

Project ID: 18680
Funded under: FP6-LIFESCIHEALTH
Country: Netherlands

Final Report Summary - POX-GENE (A combined pox-virus/lentiviral vector system to treat HIV infection. Immunisation and direct in vivo gene transfer in T lymphocytes)

Worldwide, over 40 million people are infected with HIV and AIDS is a major cause of mortality, particularly in developing countries. Currently, the only effective treatment available is highly active anti-retroviral therapy (HAART). Despite its success, it is clear that HAART cannot eradicate the virus and that sustained treatment is required. However, lifetime treatment is not always practicable, particularly in developing countries. Therefore, additional therapies are urgently required. POX GENE's goal was to combine therapeutic vaccination with direct in vivo gene transfer using a genetically modified vaccinia vector, this can then be used in developed as well as developing countries.

In this project, a pox-virus vector was created that encodes, in addition to specific HIV-1 proteins, a fully functional lentiviral vector genome delivering genes with HIV inhibitory capacity. Cells infected with modified vaccinia virus ankara (MVA) were simultaneously 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 serves 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 duration of this project important progress was made to overcome two of the main obstacles for developing an effective strategy for combined therapeutic vaccination and in vivo gene transfer.
- POX-GENE vectors were created that contain all the required information for production of retroviral vectors capable of delivering an anti-viral gene.
- An anti-viral gene was created that encodes soluble factors that effectively protect cells against infection with HIV.

Achieving these goals has been more complex than initially anticipated and hence has taken more time than expected. As a consequence the in vitro and in vivo evaluation of this strategy could only be partially completed and would require more work. Important progress has been made to optimise and characterise these test systems and the individual components of the POX-GENE strategy have been tested.

Related information

Reported by

BIOMEDICAL PRIMATE RESEARCH CENTRE
RIJSWIJK
Netherlands
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