Vaccine-induced cellular immune responses reduce plasma viral concentrations after repeated low-dose challenge with pathogenic simian immunodeficiency virus SIVmac239

Nancy A. Wilson, Jason Reed, Gnankang S. Napoe, Shari Piaskowski, Andy Szymanski, Jessica Furlott, Edna J. Gonzalez, Levi J. Yant, Nicholas J. Maness, Gemma E. May, Taeko Soma, Matthew R. Reynolds, Eva Rakasz, Richard Rudersdorf, Adrian B. McDermott, David H. O'Connor, Thomas C. Friedrich, David B. Allison, Amit Patki, Louis J. PickerDennis R. Burton, Jing Lin, Lingyi Huang, Deepa Patel, Gwendolyn Heindecker, Jiang Fan, Michael Citron, Melanie Horton, Fubao Wang, Xiaoping Liang, John W. Shiver, Danilo R. Casimiro, David I. Watkins

Research output: Contribution to journalArticle

190 Scopus citations

Abstract

The goal of an AIDS vaccine regimen designed to induce cellular immune responses should be to reduce the viral set point and preserve memory CD4 lymphocytes. Here we investigated whether vaccine-induced cellular immunity in the absence of any Env-specific antibodies can control viral replication following multiple low-dose challenges with the highly pathogenic SIVmac239 isolate. Eight Mamu-A*01-positive Indian rhesus macaques were vaccinated with simian immunodeficiency virus (SIV) gag, tat, rev, and nef using a DNA prime-adenovirus boost strategy. Peak viremia (P = 0.007) and the chronic phase set point (P = 0.0192) were significantly decreased in the vaccinated cohort, out to 1 year postinfection. Loss of CD4+ memory populations was also ameliorated in vaccinated animals. Interestingly, only one of the eight vaccinees developed Env-specific neutralizing antibodies after infection. The control observed was significantly improved over that observed in animals vaccinated with SIV gag only. Vaccine-induced cellular immune responses can, therefore, exert a measure of control over replication of the AIDS virus in the complete absence of neutralizing antibody and give us hope that a vaccine designed to induce cellular immune responses might control viral replication.

Original languageEnglish (US)
Pages (from-to)5875-5885
Number of pages11
JournalJournal of virology
Volume80
Issue number12
DOIs
StatePublished - Jun 2006

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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    Wilson, N. A., Reed, J., Napoe, G. S., Piaskowski, S., Szymanski, A., Furlott, J., Gonzalez, E. J., Yant, L. J., Maness, N. J., May, G. E., Soma, T., Reynolds, M. R., Rakasz, E., Rudersdorf, R., McDermott, A. B., O'Connor, D. H., Friedrich, T. C., Allison, D. B., Patki, A., ... Watkins, D. I. (2006). Vaccine-induced cellular immune responses reduce plasma viral concentrations after repeated low-dose challenge with pathogenic simian immunodeficiency virus SIVmac239. Journal of virology, 80(12), 5875-5885. https://doi.org/10.1128/JVI.00171-06