Eventual AIDS vaccine failure in a rhesus monkey by viral escape from cytotoxic T lymphocytes (original) (raw)

• Letter
• Published: 17 January 2002
• Jennifer Kunstman2,
• Marcelo J. Kuroda1,
• Jörn E. Schmitz1,
• Sampa Santra1,
• Fred W. Peyerl1,
• Georgia R. Krivulka1,
• Kristin Beaudry1,
• Michelle A. Lifton1,
• Darci A. Gorgone1,
• David C. Montefiori3,
• Mark G. Lewis4,
• Steven M. Wolinsky2 &
• …
• Norman L. Letvin1

Nature volume 415, pages 335–339 (2002)Cite this article

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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.

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Acknowledgements

We are grateful to T. Fu, J. Shiver, K. Reimann, C. Lord, A. Miura, R. Khunkhun, W. Wagner, S. Tyeryar, C. Crabbs and J. Yalley-Ogunro for advice, assistance and reagents.

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Authors and Affiliations

1. Department of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center, Research East Room 113, 330 Brookline Avenue, Boston, 02215, Massachusetts, USA
   Dan H. Barouch, Marcelo J. Kuroda, Jörn E. Schmitz, Sampa Santra, Fred W. Peyerl, Georgia R. Krivulka, Kristin Beaudry, Michelle A. Lifton, Darci A. Gorgone & Norman L. Letvin
2. Department of Medicine, Northwestern University Medical School, Chicago, 60611, Illinois, USA
   Jennifer Kunstman & Steven M. Wolinsky
3. Department of Surgery, Duke University Medical Center, Durham, 27710, North Carolina, USA
   David C. Montefiori
4. Southern Research Institute, Frederick, 21701, Maryland, USA
   Mark G. Lewis

Authors

1. Dan H. Barouch
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2. Jennifer Kunstman
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3. Marcelo J. Kuroda
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4. Jörn E. Schmitz
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5. Sampa Santra
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6. Fred W. Peyerl
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7. Georgia R. Krivulka
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8. Kristin Beaudry
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9. Michelle A. Lifton
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10. Darci A. Gorgone
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11. David C. Montefiori
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12. Mark G. Lewis
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13. Steven M. Wolinsky
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14. Norman L. Letvin
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Correspondence toDan H. Barouch.

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Barouch, D., Kunstman, J., Kuroda, M. et al. Eventual AIDS vaccine failure in a rhesus monkey by viral escape from cytotoxic T lymphocytes.Nature 415, 335–339 (2002). https://doi.org/10.1038/415335a

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• Received: 09 October 2001
• Accepted: 16 November 2001
• Issue Date: 17 January 2002
• DOI: https://doi.org/10.1038/415335a

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