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Journal of Virology, April 2007, p. 4137-4144, Vol. 81, No. 8
0022-538X/07/$08.00+0     doi:10.1128/JVI.02193-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Vaccine-Induced T Cells Control Reversion of AIDS Virus Immune Escape Mutants{triangledown}

Caroline S. Fernandez,1,{dagger} Miranda Z. Smith,1,{dagger} C. Jane Batten,1 Robert De Rose,1 Jeanette C. Reece,1 Erik Rollman,1 Vanessa Venturi,2 Miles P. Davenport,2 and Stephen J. Kent*

Department of Microbiology and Immunology, University of Melbourne, Melbourne, Victoria 3010, Australia,1 Department of Haematology, Prince of Wales Hospital, and Centre for Vascular Research, University of NSW, Kensington, NSW 2052, Australia2

Received 5 October 2006/ Accepted 21 January 2007

Many current-generation human immunodeficiency virus (HIV) vaccines induce specific T cells to control acute viremia, but their utility following infection with escape mutant virus is unclear. We studied reversion to wild type of an escape mutant simian-HIV in major histocompatibility complex-matched vaccinated pigtail macaques. High levels of vaccine-induced CD8+ T cells strongly correlated with maintenance of escape mutant virus during acute infection. Interestingly, in animals with lower CD8+ T-cell levels, transient reversion to wild-type virus resulted in better postacute control of viremia. Killing of wild-type virus facilitated by transient reversion outweighs the benefit of a larger CD8+ T-cell response that only maintains the less fit escape mutant virus. These findings have important implications for the further development of T-cell-based HIV vaccines where exposure to escape mutant viruses is common.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, University of Melbourne, Melbourne, Victoria 3010, Australia. Phone: 61383449939. Fax: 61383443846. E-mail: skent{at}unimelb.edu.au

{triangledown} Published ahead of print on 24 January 2007.

{dagger} C.S.F. and M.Z.S. contributed equally to the study.

Journal of Virology, April 2007, p. 4137-4144, Vol. 81, No. 8
0022-538X/07/$08.00+0     doi:10.1128/JVI.02193-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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