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Journal of Virology, March 2007, p. 2838-2848, Vol. 81, No. 6
0022-538X/07/$08.00+0     doi:10.1128/JVI.01914-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Understanding the Failure of CD8+ T-Cell Vaccination against Simian/Human Immunodeficiency Virus{triangledown}

Rob J. De Boer*

Theoretical Biology UU, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands

Received 2 September 2006/ Accepted 13 December 2006

Although CD8+ T cells play an important role in controlling viral infections, boosting specific CD8+ T cells by prophylactic vaccination with simian immunodeficiency virus (SIV) epitopes fails to provide sterilizing immunity. Viral replication rates and viral contraction rates after the peak viremia hardly depend on the presence of memory CD8+ T cells. To study these paradoxical findings, we parameterize novel mathematical models for acute SIV and human immunodeficiency virus infection. These models explain that failure of vaccination is due to the fact that effector/target ratios are too low during the viral expansion phase. Because CD8+ T cells require cell-to-cell contacts, immune protection requires high effector/target ratios at the primary site of infection. Effector/target ratios become favorable for immune control at the time of the peak in the viral load when the virus becomes limited by other factors, such as the availability of uninfected target cells. At the viral set point, effector/target ratios are much higher, and perturbations of the number of CD8+ effector cells have a large impact on the viral load. Such protective effector/target ratios are difficult to achieve with nucleic acid- or protein-based vaccines.

* Mailing address: Theoretical Biology UU, Padualaan 8, 3584 CH Utrecht, The Netherlands. Phone: 31 30 253 7560. Fax: 31 30 251 3655. E-mail: r.j.deboer{at}bio.uu.nl.

{triangledown} Published ahead of print on 3 January 2007.

Journal of Virology, March 2007, p. 2838-2848, Vol. 81, No. 6
0022-538X/07/$08.00+0     doi:10.1128/JVI.01914-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Ganusov, V. V., De Boer, R. J. (2008). Estimating In Vivo Death Rates of Targets due to CD8 T-Cell-Mediated Killing. J. Virol. 82: 11749-11757 [Abstract] [Full Text]  


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