Protection against simian/human immunodeficiency virus (SHIV) 89.6P in macaques after coimmunization with SHIV antigen and IL-15 plasmid

Jean D. Boyer, Tara M. Robinson, Michele A. Kutzler, Gordon Vansant, David A. Hokey, Sanjeev Kumar, Rose Parkinson, Ling Wu, Maninder K. Sidhu, George N. Pavlakis, Barbara K. Felber, Charles Brown, Peter Silvera, Mark G. Lewis, Joseph Monforte, Thomas A. Waldmann, John Eldridge, David B. Weiner

Research output: Contribution to journalArticle

Abstract

The cell-mediated immune profile induced by a recombinant DNA vaccine was assessed in the simian/HIV (SHIV) and macaque model. The vaccine strategy included coimmunization of a DNA-based vaccine alone or in combination with an optimized plasmid encoding macaque IL-15 (pmacIL-15). We observed strong induction of vaccine-specific IFN-γ-producing CD8+ and CD4 + effector T cells in the vaccination groups. Animals were subsequently challenged with 89.6p. The vaccine groups were protected from ongoing infection, and the IL-15 covaccinated group showed a more rapidly controlled infection than the group treated with DNA vaccine alone. Lymphocytes isolated from the group covaccinated with pmacIL-15 had higher cellular proliferative responses than lymphocytes isolated from the macaques that received SHIV DNA alone. Vaccine antigen activation of lymphocytes was also studied for a series of immunological molecules. Although mRNA for IFN-γ was up-regulated after antigen stimulation, the inflammatory molecules IL-8 and MMP-9 were down-regulated. These observed immune profiles are potentially reflective of the ability of the different groups to control SHIV replication. This study demonstrates that an optimized IL-15 immune adjuvant delivered with a DNA vaccine can impact the cellular immune profile in nonhuman primates and lead to enhanced suppression of viral replication.

Original languageEnglish (US)
Pages (from-to)18648-18653
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number47
DOIs
StatePublished - Nov 20 2007
Externally publishedYes

Keywords

  • Cytokine adjuvant
  • HIV vaccine
  • Immune response
  • T cell immunity

ASJC Scopus subject areas

  • General

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  • Cite this

    Boyer, J. D., Robinson, T. M., Kutzler, M. A., Vansant, G., Hokey, D. A., Kumar, S., Parkinson, R., Wu, L., Sidhu, M. K., Pavlakis, G. N., Felber, B. K., Brown, C., Silvera, P., Lewis, M. G., Monforte, J., Waldmann, T. A., Eldridge, J., & Weiner, D. B. (2007). Protection against simian/human immunodeficiency virus (SHIV) 89.6P in macaques after coimmunization with SHIV antigen and IL-15 plasmid. Proceedings of the National Academy of Sciences of the United States of America, 104(47), 18648-18653. https://doi.org/10.1073/pnas.0709198104