Therapeutic vaccination with simian immunodeficiency virus (SIV)-DNA+IL-12 or IL-15 induces distinct CD8 memory subsets in SIV-infected macaques

Rabih Halwani, Jean D. Boyer, Bader Yassine-Diab, Elias K. Haddad, Tara M. Robinson, Sanjeev Kumar, Rose Parkinson, Ling Wu, Maninder K. Sidhu, Rebecca Phillipson-Weiner, George N. Pavlakis, Barbara K. Felber, Mark G. Lewis, Anding Shen, Robert F. Siliciano, David B. Werner, Rafick Pierre Sekaly

Research output: Contribution to journalArticlepeer-review

Abstract

DNA vaccination is an invaluable approach for immune therapy in that it lacks vector interference and thus permits repeated vaccination boosts. However, by themselves, DNA-based vaccines are typically poor inducers of Ag-specific immunity in humans and non-human primates. Cytokines, such as IL-12 and IL-15, have been shown to be potent adjuvants for the induction and maintenance of cellular immune responses, in particular during HIV infection. In this study, we examined the ability of therapeutic vaccination with SIV-DNA+IL-12 or IL-15 as molecular adjuvants to improve DNA vaccine potency and to enhance memory immune responses in SIV-infected macaques. Our results demonstrate that incorporating IL-12 into the vaccine induces SIV-specific CD8 effector memory T cell (T EM) functional responses and enhances the capacity of IFN-γ-producing CD8 TEM cells to produce TNF. Lower levels of PD-1 were expressed on T cells acquiring dual function upon vaccination as compared with mono-functional CD8 TEM cells. Finally, a boost with SIV-DNA+IL-15 triggered most T cell memory subsets in macaques primed with either DNA-SIV or placebo but only CD8 TEM in macaques primed with SIV-DNA+IL-12. These results indicate that plasmid IL-12 and IL-15 cytokines represent a significant addition to enhance the ability of therapeutic DNA vaccines to induce better immunity.

Original languageEnglish (US)
Pages (from-to)7969-7979
Number of pages11
JournalJournal of Immunology
Volume180
Issue number12
DOIs
StatePublished - 2008

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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