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Journal of Virology, November 2006, p. 10950-10956, Vol. 80, No. 22
0022-538X/06/$08.00+0     doi:10.1128/JVI.01458-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Virus-Specific Cellular Immune Correlates of Survival in Vaccinated Monkeys after Simian Immunodeficiency Virus Challenge{triangledown}

Yue Sun,1 Jörn E. Schmitz,1 Adam P. Buzby,1 Brianne R. Barker,1 Srinivas S. Rao,2 Ling Xu,2 Zhi-yong Yang,2 John R. Mascola,2 Gary J. Nabel,2 and Norman L. Letvin1,2*

Division of Viral Pathogenesis, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02115,1 Vaccine Research Center, National Institutes of Allergy and Infectious Disease, National Institutes of Health, Bethesda, Maryland 208922

Received 10 July 2006/ Accepted 23 August 2006

Understanding the characteristics of the virus-specific T-lymphocyte response that will confer optimal protection against the clinical progression of AIDS will inform the development of an effective cellular immunity-based human immunodeficiency virus vaccine. We have recently shown that survival in plasmid DNA-primed/recombinant adenovirus-boosted rhesus monkeys that are challenged with the simian immunodeficiency virus SIVmac251 is associated with the preservation postchallenge of central memory CD4+ T lymphocytes and robust gamma interferon (IFN-{gamma})-producing SIV-specific CD8+ and CD4+ T-lymphocyte responses. The present studies were initiated to extend these observations to determine which virus-specific T-lymphocyte subpopulations play a primary role in controlling disease progression and to characterize the functional repertoire of these cells. We show that the preservation of the SIV-specific central memory CD8+ T-lymphocyte population and a linked SIV-specific CD4+ T-lymphocyte response are associated with prolonged survival in vaccinated monkeys following challenge. Furthermore, we demonstrate that SIV-specific IFN-{gamma}-, tumor necrosis factor alpha-, and interleukin-2-producing T lymphocytes are all comparably associated with protection against disease progression. These findings underscore the contribution of virus-specific central memory T lymphocytes to controlling clinical progression in vaccinated individuals following a primate immunodeficiency virus infection.

* Corresponding author. Mailing address: Division of Viral Pathogenesis, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, RE113, Boston, MA 02215. Phone: (617) 667-2766. Fax: (617) 667-8210. E-mail: nletvin{at}bidmc.harvard.edu.

{triangledown} Published ahead of print on 30 August 2006.

Journal of Virology, November 2006, p. 10950-10956, Vol. 80, No. 22
0022-538X/06/$08.00+0     doi:10.1128/JVI.01458-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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