Eventual AIDS vaccine failure in a rhesus monkey by viral escape from cytotoxic T lymphocytes

Dan H. Barouch (), Jennifer Kunstman, Marcelo J. Kuroda, Jörn E. Schmitz, Sampa Santra, Fred W. Peyerl, Georgia R. Krivulka, Kristin Beaudry, Michelle A. Lifton, Darci A. Gorgone, David C. Montefiori, Mark G. Lewis, Steven M. Wolinsky and Norman L. Letvin
Additional contact information
Dan H. Barouch: Harvard Medical School, Beth Israel Deaconess Medical Center, Research East Room 113
Jennifer Kunstman: Northwestern University Medical School
Marcelo J. Kuroda: Harvard Medical School, Beth Israel Deaconess Medical Center, Research East Room 113
Jörn E. Schmitz: Harvard Medical School, Beth Israel Deaconess Medical Center, Research East Room 113
Sampa Santra: Harvard Medical School, Beth Israel Deaconess Medical Center, Research East Room 113
Fred W. Peyerl: Harvard Medical School, Beth Israel Deaconess Medical Center, Research East Room 113
Georgia R. Krivulka: Harvard Medical School, Beth Israel Deaconess Medical Center, Research East Room 113
Kristin Beaudry: Harvard Medical School, Beth Israel Deaconess Medical Center, Research East Room 113
Michelle A. Lifton: Harvard Medical School, Beth Israel Deaconess Medical Center, Research East Room 113
Darci A. Gorgone: Harvard Medical School, Beth Israel Deaconess Medical Center, Research East Room 113
David C. Montefiori: Duke University Medical Center
Mark G. Lewis: Southern Research Institute
Steven M. Wolinsky: Northwestern University Medical School
Norman L. Letvin: Harvard Medical School, Beth Israel Deaconess Medical Center, Research East Room 113

Nature, 2002, vol. 415, issue 6869, 335-339

Abstract: Abstract Potent virus-specific cytotoxic T lymphocyte (CTL) responses elicited by candidate AIDS vaccines have recently been shown to control viral replication and prevent clinical disease progression after pathogenic viral challenges in rhesus monkeys1,2,3,4. Here we show that viral escape from CTL recognition can result in the eventual failure of this partial immune protection. Viral mutations that escape from CTL recognition have been previously described in humans infected with human immunodeficiency virus (HIV)5,6,7,8,9,10 and monkeys infected with simian immunodeficiency virus (SIV)11,12,13. In a cohort of rhesus monkeys that were vaccinated and subsequently infected with a pathogenic hybrid simian–human immunodeficiency virus (SHIV), the frequency of viral sequence mutations within CTL epitopes correlated with the level of viral replication. A single nucleotide mutation within an immunodominant Gag CTL epitope in an animal with undetectable plasma viral RNA resulted in viral escape from CTLs, a burst of viral replication, clinical disease progression, and death from AIDS-related complications. These data indicate that viral escape from CTL recognition may be a major limitation of the CTL-based AIDS vaccines that are likely to be administered to large human populations over the next several years.

Date: 2002
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DOI: 10.1038/415335a

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