This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Davenport, M. P.
Right arrow Articles by Perelson, A. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Davenport, M. P.
Right arrow Articles by Perelson, A. S.

 Previous Article  |  Next Article 

Journal of Virology, October 2004, p. 11340-11351, Vol. 78, No. 20
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.20.11340-11351.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Predicting the Impact of a Nonsterilizing Vaccine against Human Immunodeficiency Virus

Miles P. Davenport,1,2 Ruy M. Ribeiro,2 Dennis L. Chao,3 and Alan S. Perelson2*

Department of Haematology, Prince of Wales Hospital, and Centre for Vascular Research, University of New South Wales, Kensington, New South Wales, Australia,1 Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos,2 Department of Computer Science, University of New Mexico, Albuquerque New Mexico3

Received 13 August 2003/ Accepted 4 June 2004

Studies of human immunodeficiency virus (HIV) vaccines in animal models suggest that it is difficult to induce complete protection from infection (sterilizing immunity) but that it is possible to reduce the viral load and to slow or prevent disease progression following infection. We have developed an age-structured epidemiological model of the effects of a disease-modifying HIV vaccine that incorporates the intrahost dynamics of infection, a transmission rate and host mortality that depend on the viral load, the possible evolution and transmission of vaccine escape mutant viruses, a finite duration of vaccine protection, and possible changes in sexual behavior. Using this model, we investigated the long-term outcome of a disease-modifying vaccine and utilized uncertainty analysis to quantify the effects of our lack of precise knowledge of various parameters. Our results suggest that the extent of viral load reduction in vaccinated infected individuals (compared to unvaccinated individuals) is the key predictor of vaccine efficacy. Reductions in viral load of about 1 log10 copies ml–1 would be sufficient to significantly reduce HIV-associated mortality in the first 20 years after the introduction of vaccination. Changes in sexual risk behavior also had a strong impact on the epidemic outcome. The impact of vaccination is dependent on the population in which it is used, with disease-modifying vaccines predicted to have the most impact in areas of low prevalence and rapid epidemic growth. Surprisingly, the extent to which vaccination alters disease progression, the rate of generation of escape mutants, and the transmission of escape mutants are predicted to have only a weak impact on the epidemic outcome over the first 25 years after the introduction of a vaccine.

* Corresponding author. Mailing address: MS-K710, T-10, Theoretical Biology & Biophysics Group, Los Alamos National Laboratory, Los Alamos, NM 87545. Phone: (505) 667-6829. Fax: (505) 665-3493. E-mail: asp{at}lanl.gov.

Journal of Virology, October 2004, p. 11340-11351, Vol. 78, No. 20
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.20.11340-11351.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Whitney, J. B., Luedemann, C., Hraber, P., Rao, S. S., Mascola, J. R., Nabel, G. J., Letvin, N. L. (2009). T-Cell Vaccination Reduces Simian Immunodeficiency Virus Levels in Semen. J. Virol. 83: 10840-10843 [Abstract] [Full Text]  
  • Kitabwalla, M., Ansari, A. A., Villinger, F., Akeefe, H., Conner, A. P., Mayne, A. E., Hildreth, J. E. K. (2008). Delipidated Retroviruses as Potential Autologous Therapeutic Vaccines--A Pilot Experiment. Exp. Biol. Med. 233: 732-740 [Abstract] [Full Text]  
  • Berry, I. M., Ribeiro, R., Kothari, M., Athreya, G., Daniels, M., Lee, H. Y., Bruno, W., Leitner, T. (2007). Unequal Evolutionary Rates in the Human Immunodeficiency Virus Type 1 (HIV-1) Pandemic: the Evolutionary Rate of HIV-1 Slows Down When the Epidemic Rate Increases. J. Virol. 81: 10625-10635 [Abstract] [Full Text]  
  • Stover, J., Bollinger, L., Hecht, R., Williams, C., Roca, E. (2007). The Impact Of An AIDS Vaccine In Developing Countries: A New Model And Initial Results. Health Aff (Millwood) 26: 1147-1158 [Abstract] [Full Text]  
  • De Boer, R. J. (2007). Understanding the Failure of CD8+ T-Cell Vaccination against Simian/Human Immunodeficiency Virus. J. Virol. 81: 2838-2848 [Abstract] [Full Text]  
  • Hanke, T., McMichael, A. J., Dorrell, L. (2007). Clinical experience with plasmid DNA- and modified vaccinia virus Ankara-vectored human immunodeficiency virus type 1 clade A vaccine focusing on T-cell induction. J. Gen. Virol. 88: 1-12 [Abstract] [Full Text]  
  • Krebs, K. C., Jin, Z., Rudersdorf, R., Hughes, A. L., O'Connor, D. H. (2005). Unusually High Frequency MHC Class I Alleles in Mauritian Origin Cynomolgus Macaques. J. Immunol. 175: 5230-5239 [Abstract] [Full Text]  
  • Davenport, M. P., Zhang, L., Bagchi, A., Fridman, A., Fu, T.-M., Schleif, W., Shiver, J. W., Ribeiro, R. M., Perelson, A. S. (2005). High-Potency Human Immunodeficiency Virus Vaccination Leads to Delayed and Reduced CD8+ T-Cell Expansion but Improved Virus Control. J. Virol. 79: 10059-10062 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»