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J. Virol. doi:10.1128/JVI.02242-07
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Expansion and exhaustion of T cell responses during mutational escape from long-term viral control in two DNA/MVA vaccinated and SHIV-89.6P challenged macaques

Emory Vaccine Center, Emory University School of Medicine, 954 Gatewood Road, Atlanta, GA 30329, USA; Yerkes National Primate Research Center, 954 Gatewood Road, Atlanta, GA 30329, USA; Department of Microbiology and Immunology of Emory University School of Medicine, Emory University, Atlanta, GA 30322, USA

^* To whom correspondence should be addressed. Email: hrobins{at}rmy.emory.edu.

	Abstract

Here, we monitor the temporal breadth, frequency and function of anti-viral CD4 and CD8 T cells in 2 of 22 DNA/MVA vaccinated macaques that lost control of a SHIV-89.6P challenge by 196 weeks post challenge. Our results show both mutation and exhaustion contributing to escape. With the reappearance of viremia, responding CD8 and CD4 T cells underwent an initial increase, and then loss in breadth and frequency. Anti-viral IFN- and IL-2 co-producing cells were lost before IFN--producing cells, and CD4 cells before CD8 cells. At euthanasia, all CD8, but no CD4, Gag epitopes detected during long term control contained mutations.