Induction of AIDS virus-specific CTL activity in fresh, unstimulated peripheral blood lymphocytes from rhesus macaques vaccinated with a DNA prime/modified vaccinia virus Ankara boost regimen

Todd M. Allen, Thorsten U. Vogel, Deborah H. Fuller, Bianca R. Mothé, Susan Steffen, Jon E. Boyson, Tim Shipley, Jim Fuller, Tomas Hanke, Alessandro Sette, John D. Altman, Bernard Moss, Andrew J. McMichael, David I. Watkins

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245 Scopus citations

Abstract

The observed role of CTL in the containment of AIDS virus replication suggests that an effective HIV vaccine will be required to generate strong CTL responses. Because epitope-based vaccines offer several potential advantages for inducing strong, multispecific CTL responses, we tested the ability of an epitope-based DNA prime/modified vaccinia virus Ankara (MVA) boost vaccine to induce CTL responses against a single SIVgag CTL epitope. As assessed using both 51Cr release assays and tetramer staining of in vitro stimulated PBMC, DNA vaccinations administered to the skin with the gene gun induced and progressively increased p11C, C → M (CTPYDINQM)-specific CD8+ T lymphocyte responses in six of six Mamu-A*01+ rhesus macaques. Tetramer staining of fresh, unstimulated PBMC from two of the DNA-vaccinated animals indicated that as much as 0.4.% of all CD3+/CD8α+ T lymphocytes were specific for the SIVgag CTL epitope. Administration of MVA expressing the SIVgag CTL epitope further boosted these responses, such that 0.8-20.0% of CD3+/CD8α+ T lymphocytes in fresh, unstimulated PBMC were now Ag specific. Enzyme-linked immunospot assays confirmed this high frequency of Ag-specific cells, and intracellular IFN-γ staining demonstrated that the majority of these cells produced IFN-γ after peptide stimulation. Moreover, direct ex vivo SIV-specific cytotoxic activity could be detected in PBMC from live of the six DNA/MVA-vaccinated animals, indicating that this epitope-based DNA prime/MVA boost regimen represents a potent method for inducing high levels of functionally active, Ag-specific CD8+ T lymphocytes in non-human primates.

Original languageEnglish (US)
Pages (from-to)4968-4978
Number of pages11
JournalJournal of Immunology
Volume164
Issue number9
DOIs
StatePublished - May 1 2000

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Allen, T. M., Vogel, T. U., Fuller, D. H., Mothé, B. R., Steffen, S., Boyson, J. E., Shipley, T., Fuller, J., Hanke, T., Sette, A., Altman, J. D., Moss, B., McMichael, A. J., & Watkins, D. I. (2000). Induction of AIDS virus-specific CTL activity in fresh, unstimulated peripheral blood lymphocytes from rhesus macaques vaccinated with a DNA prime/modified vaccinia virus Ankara boost regimen. Journal of Immunology, 164(9), 4968-4978. https://doi.org/10.4049/jimmunol.164.9.4968