Skip to main content
Download PDF

Volume 6 Supplement 2

Frontiers of Retrovirology: Complex retroviruses, retroelements and their hosts

Novel vaccine and gene therapy approaches against HIV-AIDS

Retrovirology volume 6, Article number: I24 (2009) Cite this article

The design of novel anti-HIV vaccination and gene therapy strategies will be presented, including pilot experiments in animal models. Our gene therapy approach uses the RNA interference (RNAi) machinery to make human cells resistant to HIV-1. The problem of viral escape and the control of viral escape by means of a combination-RNAi therapy will be discussed. A humanized mouse model has been set up as pre-clinical test system to address the safety and efficacy of lentiviral vector-delivered RNAi cassettes. Our vaccination approach deals with the novel concept of a conditional-live virus that can be turned on and off at will. Live-attenuated virus confers the most potent protection against wild-type virus challenge in the SIV/macaque vaccination model. However, such a vaccine is not pursued because of safety reasons as the vaccine virus persists and may evolve into a pathogenic variant. We therefore designed an SIVmac239Δnef variant that is dependent on doxycycline for replication by replacing the natural Tat/TAR transcription mechanism by the Tet-system for inducible gene expression. Replication of this virus can be switched off after vaccination, which will prevent evolution. The first rhesus macaque test yielded a marked vaccine effect. This new conditional-live virus will be a useful tool to identify the correlates of protection by this vaccine strategy.

Author information

Authors and Affiliations

  1. Laboratory of Experimental Virology, University of Amsterdam, the Netherlands

    A Das, W Kleibeuker, B Klaver, K von Eije, YP Liu, O ter Brake, M Centlivre & B Berkhout

  2. Department of Cell Biology, University of Amsterdam, the Netherlands

    N Legrand

  3. NIBSC, Division of Retrovirology, Potters Bar, Herts, UK

    N Berry, H Tudor, M Page, M Robinson, R Quartey-Papafio, W Elsley, B Li, R Stebbings & N Almond

  4. Division of Cellular and Molecular Medicine, St. George's, University of London, UK

    M Manoussaka & M Cranage

Authors
  1. A Das
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. W Kleibeuker
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. B Klaver
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. K von Eije
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. YP Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. O ter Brake
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. M Centlivre
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. N Legrand
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. N Berry
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. H Tudor
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. M Page
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. M Robinson
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. R Quartey-Papafio
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. W Elsley
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. B Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. M Manoussaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. R Stebbings
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. M Cranage
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. N Almond
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. B Berkhout
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/2.0 ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Reprints and Permissions

About this article

Cite this article

Das, A., Kleibeuker, W., Klaver, B. et al. Novel vaccine and gene therapy approaches against HIV-AIDS. Retrovirology 6 (Suppl 2), I24 (2009). https://doi.org/10.1186/1742-4690-6-S2-I24

Download citation

  • Published:

  • DOI: https://doi.org/10.1186/1742-4690-6-S2-I24

Keywords

  • Doxycycline
  • Pathogenic Variant
  • Inducible Gene Expression
  • Humanize Mouse
  • Vaccine Strategy

Retrovirology

ISSN: 1742-4690

Contact us