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Journal of Virology, March 2005, p. 3855-3858, Vol. 79, No. 6
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.6.3855-3858.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Improving the Safety of a Conditional-Live Human Immunodeficiency Virus Type 1 Vaccine by Controlling both Gene Expression and Cell Entry

Atze T. Das,1 Chris E. Baldwin,1,2 Monique Vink,1 and Ben Berkhout1*

Department of Human Retrovirology,1 International Antiviral Therapy Evaluation Center, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands2

Received 28 September 2004/ Accepted 25 October 2004

Live attenuated human immunodeficiency virus type 1 (HIV-1) vaccines are considered unsafe because faster-replicating pathogenic virus variants may evolve after vaccination. We previously presented a conditional-live HIV-1 variant of which replication can be switched off as an alternative vaccination strategy. To improve the safety of such a vaccine, we constructed a new HIV-1 variant that depends not only on doxycycline for gene expression but also on the T20 peptide for cell entry. Replication of this virus can be limited to the level required to induce the immune system by transient administration of doxycycline and T20. Subsequent withdrawal of these inducers efficiently blocks viral replication and evolution.

* Corresponding author. Mailing address: Department of Human Retrovirology, Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands. Phone: (31-20) 5664822. Fax: (31-20) 6916531. E-mail: b.berkhout{at}amc.uva.nl.

Journal of Virology, March 2005, p. 3855-3858, Vol. 79, No. 6
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.6.3855-3858.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Das, A. T., Klaver, B., Harwig, A., Vink, M., Ooms, M., Centlivre, M., Berkhout, B. (2007). Construction of a Doxycycline-Dependent Simian Immunodeficiency Virus Reveals a Nontranscriptional Function of Tat in Viral Replication. J. Virol. 81: 11159-11169 [Abstract] [Full Text]  
  • Zhou, X., Vink, M., Klaver, B., Verhoef, K., Marzio, G., Das, A. T., Berkhout, B. (2006). The Genetic Stability of a Conditional Live HIV-1 Variant Can Be Improved by Mutations in the Tet-On Regulatory System That Restrain Evolution. J. Biol. Chem. 281: 17084-17091 [Abstract] [Full Text]  


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