Attenuation of simian immunodeficiency virus SIVmac239 infection by prophylactic immunization with DNA and recombinant adenoviral vaccine vectors expressing Gag

Danilo R. Casimiro, Fubao Wang, William A. Schleif, Xiaoping Liang, Zhi Qiang Zhang, Timothy W. Tobery, Mary Ellen Davies, Adrian B. McDermott, David H. O'Connor, Arthur Fridman, Ansu Bagchi, Lynda G. Tussey, Andrew J. Bett, Adam C. Finnefrock, Tong Ming Fu, Aimin Tang, Keith A. Wilson, Minchun Chen, Helen C. Perry, Gwendolyn J. HeideckerDaniel C. Freed, Anthony Carella, Kara S. Punt, Kara J. Sykes, Lingyi Huang, Virginia I. Ausensi, Margaret Bachinsky, Usha Sadasivan-Nair, David I. Watkins, Emilio A. Emini, John W. Shiver

Research output: Contribution to journalArticle

199 Scopus citations

Abstract

The prophylactic efficacy of DNA and replication-incompetent adenovirus serotype 5 (Ad5) vaccine vectors expressing simian immunodeficiency virus (SIV) Gag was examined in rhesus macaques using an SFVmac239 challenge. Cohorts of either Mamu-A*01(+) or Mamu-A*01(-) macaques were immunized with a DNA prime-Ad5 boost regimen; for comparison, a third cohort consisting of Mamu-A*01(+) monkeys was immunized using the Ad5 vector alone for both prime and boost. All animals, along with unvaccinated control cohorts of Mamu-A*01(+) and Mamu-A*01(-) macaques, were challenged intrarectally with SFVmac239. Viral loads were measured in both peripheral and lymphoid compartments. Only the DNA prime-Ad5-boosted Mamu-A*01(+) cohort exhibited a notable reduction in peak plasma viral load (sevenfold) as well as in early set-point viral burdens in both plasma and lymphoid tissues (10-fold) relative to those observed in the control monkeys sharing the same Mamu-A*01 allele. The degree of control in each animal correlated with the levels of Gag-specific immunity before virus challenge. However, virus control was short-lived, and indications of viral escape were evident as early as 6 months postinfection. The implications of these results in vaccine design and clinical testing are discussed.

Original languageEnglish (US)
Pages (from-to)15547-15555
Number of pages9
JournalJournal of virology
Volume79
Issue number24
DOIs
StatePublished - Dec 2005

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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    Casimiro, D. R., Wang, F., Schleif, W. A., Liang, X., Zhang, Z. Q., Tobery, T. W., Davies, M. E., McDermott, A. B., O'Connor, D. H., Fridman, A., Bagchi, A., Tussey, L. G., Bett, A. J., Finnefrock, A. C., Fu, T. M., Tang, A., Wilson, K. A., Chen, M., Perry, H. C., ... Shiver, J. W. (2005). Attenuation of simian immunodeficiency virus SIVmac239 infection by prophylactic immunization with DNA and recombinant adenoviral vaccine vectors expressing Gag. Journal of virology, 79(24), 15547-15555. https://doi.org/10.1128/JVI.79.24.15547-15555.2005