Macaques vaccinated with live-attenuated SIV control replication of heterologous virus

Matthew R. Reynolds, Andrea M. Weiler, Kim L. Weisgrau, Shari M. Piaskowski, Jessica R. Furlott, Jason T. Weinfurter, Masahiko Kaizu, Taeko Soma, Enrique J. León, Caitlin MacNair, Dan P. Leaman, Michael B. Zwick, Emma Gostick, Solomon K. Musani, David A. Price, Thomas C. Friedrich, Eva G. Rakasz, Nancy A. Wilson, Adrian B. McDermott, Rosanne BoyleDavid B. Allison, Dennis R. Burton, Wayne C. Koff, David Watkins

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118 Scopus citations

Abstract

An effective AIDS vaccine will need to protect against globally diverse isolates of HIV. To address this issue in macaques, we administered a live-attenuated simian immunodeficiency virus (SIV) vaccine and challenged with a highly pathogenic heterologous isolate. Vaccinees reduced viral replication by ∼2 logs between weeks 2-32 (P ≤ 0.049) postchallenge. Remarkably, vaccinees expressing MHC-I (MHC class I) alleles previously associated with viral control completely suppressed acute phase replication of the challenge virus, implicating CD8 + T cells in this control. Furthermore, transient depletion of peripheral CD8 + lymphocytes in four vaccinees during the chronic phase resulted in an increase in virus replication. In two of these animals, the recrudescent virus population contained only the vaccine strain and not the challenge virus. Alarmingly, however, we found evidence of recombinant viruses emerging in some of the vaccinated animals. This finding argues strongly against an attenuated virus vaccine as a solution to the AIDS epidemic. On a more positive note, our results suggest that MHC-I-restricted CD8 + T cells contribute to the protection induced by the live-attenuated SIV vaccine and demonstrate that vaccine- induced CD8 + T cell responses can control replication of heterologous challenge viruses.

Original languageEnglish
Pages (from-to)2537-2550
Number of pages14
JournalJournal of Experimental Medicine
Volume205
Issue number11
DOIs
StatePublished - Oct 27 2008
Externally publishedYes

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ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Medicine(all)

Cite this

Reynolds, M. R., Weiler, A. M., Weisgrau, K. L., Piaskowski, S. M., Furlott, J. R., Weinfurter, J. T., Kaizu, M., Soma, T., León, E. J., MacNair, C., Leaman, D. P., Zwick, M. B., Gostick, E., Musani, S. K., Price, D. A., Friedrich, T. C., Rakasz, E. G., Wilson, N. A., McDermott, A. B., ... Watkins, D. (2008). Macaques vaccinated with live-attenuated SIV control replication of heterologous virus. Journal of Experimental Medicine, 205(11), 2537-2550. https://doi.org/10.1084/jem.20081524