Co-immunization with IL-15 enhances cellular immune responses induced by a vif-deleted simian immunodeficiency virus proviral DNA vaccine and confers partial protection against vaginal challenge with SIVmac251

Robert A. Dubie, Saipiroon Maksaereekul, Barbara Shacklett, Donna Lemongello, Kelly S. Cole, Francois Villinger, Shelley A. Blozis, Paul A Luciw, Ellen E. Sparger

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Simian immunodeficiency virus (SIV) infection of rhesus macaques is a valuable animal model for human immunodeficiency virus (HIV)-1 vaccine development. Our laboratory recently described the immunogenicity and limited efficacy of a vif-deleted SIVmac239 proviral DNA (SIV/CMVΔvif) vaccine. The current report characterizes immunogenicity and efficacy for the SIV/CMVΔvif proviral DNA vaccine when co-inoculated with an optimized rhesus interleukin (rIL)-15 expression plasmid. Macaques co-inoculated with rIL-15 and SIV/CMVΔvif proviral plasmids showed significantly improved SIV-specific CD8 T cell immunity characterized by increased IFN-γ ELISPOT and polyfunctional CD8 T cell responses. Furthermore, these animals demonstrated a sustained suppression of plasma virus loads after multiple low dose vaginal challenges with pathogenic SIVmac251. Importantly, SIV-specific cellular responses were greater in immunized animals compared to unvaccinated controls during the initial 12 weeks after challenge. Taken together, these findings support the use of IL-15 as an adjuvant in prophylactic anti-HIV vaccine strategies.

Original languageEnglish (US)
Pages (from-to)109-121
Number of pages13
JournalVirology
Volume386
Issue number1
DOIs
StatePublished - Mar 30 2009

Keywords

  • DNA vaccine
  • Interleukin-15
  • SIV
  • vif

ASJC Scopus subject areas

  • Virology

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