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

• Authors: Robert A. Dubie, University of California Davis; Saipiroon Maksaereekul, University of California Davis; Barbara L. Shacklett, University of California Davis; Donna Lemongello, University of California Davis; Kelly S. Cole, University of Pittsburgh; Francois Villinger, Emory University; Shelley A. Blozis, University of California Davis; Paul A. Luciw, University of California Davis; Ellen E. Sparger, University of California Davis
• Journal Title: Virology
• Volume: Volume 386, Number 1
• Publisher: Elsevier | 2009-03-30, Pages 109-121
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1016/j.virol.2009.01.007
• Subjects: Biology, Virology; Biology, Genetics
• Keywords: Science & Technology; Life Sciences & Biomedicine; Virology; SIV; DNA vaccine; vif; Interleukin-15; CD8(+) T-CELLS; RHESUS MACAQUES; DISEASE PROGRESSION; INFECTED MACAQUES; PATHOGENIC SIVMAC251; NONHUMAN-PRIMATES; MUCOSAL CHALLENGE; AIDS VACCINE; INTERLEUKIN-15; REPLICATION

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.