The Journal of Experimental Medicine
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Published online 30 May 2006 doi:10.1084/jem.20060657
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 203, Number 6, 1533-1541
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ARTICLE

 Vaccination preserves CD4 memory T cells during acute simian immunodeficiency virus challenge

Joseph J. Mattapallil1, Daniel C. Douek1, Alicia Buckler-White2, David Montefiori3, Norman L. Letvin4, Gary J. Nabel1, and Mario Roederer1

1 Vaccine Research Center and 2 Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Disease (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892
3 Duke University Medical Center, Durham, NC 27710
4 Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215

CORRESPONDENCE M. Roederer: roederer{at}nih.gov

Acute simian immunodeficiency virus (SIV)/human immunodeficiency virus infection is accompanied by a massive destruction of CD4 memory T cells across all the tissue compartments. These early events set the course toward disease progression and immunodeficiency. Here, we demonstrate that prior vaccination reduces this destruction during acute SIV Mac251 infection, leading to better survival and long-term outcome. Systemic vaccination with a DNA-prime recombinant adenovirus boost regimen preserved memory CD4 T cells throughout the body. The vaccine regimen induced broad CD4 and CD8 T cell responses in all tissues examined and, importantly, induced antibodies that neutralized the primary isolate of SIV used for challenge. Finally, we demonstrate that the extent of preservation of the CD4 memory compartment during the acute phase provides a strong predictor for subsequent progression to death. Our data provide a mechanism to explain clinical observations that acute-phase viral loads predict long-term disease progression and underscore the need for interventions that protect against early destruction of CD4 memory T cells during acute infection.

Abbreviations used: qPCR, quantitative PCR; rAd, recombinant adenovirus; SIV, simian immunodeficiency virus; TCLA, T cell line–adapted; VL, viral load.


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