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.
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/CMVDelta vif) vaccine. The current report characterizes immunogenicity and efficacy for the SIV/CMVDelta vif proviral DNA vaccine when co-inoculated with an optimized rhesus interleukin (rIL)-15 expression plasmid. Macaques co-inoculated with rIL-15 and SIV/CMVDelta vif proviral plasmids showed significantly improved SIV-specific CD8 T cell immunity characterized by increased IFN-gamma 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.
Dubie
Robert A
RA
Department of Medicine and Epidemiology, 2108 Tupper Hall, School of Veterinary Medicine, University of California, Davis, CA 95616, USA.
Maksaereekul
Saipiroon
S
Shacklett
Barbara L
BL
Lemongello
Donna
D
Cole
Kelly S
KS
Villinger
Francois
F
Blozis
Shelley A
SA
Luciw
Paul A
PA
Sparger
Ellen E
EE
D000276:Adjuvants, Immunologic / Q000235:genetics / Q000494:pharmacology*; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D017353:Gene Deletion; D016346:Gene Products, vif / Q000235:genetics; D007371:Interferon-gamma / Q000378:metabolism; D019409:Interleukin-15 / Q000235:genetics / Q000494:pharmacology*; D008253:Macaca mulatta; D010957:Plasmids; D011533:Proviruses / Q000235:genetics / Q000276:immunology*; D018449:SAIDS Vaccines / Q000235:genetics / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000517:prevention & control*; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology*; D019562:Viral Load
D000276:Adjuvants, Immunologic; D016346:Gene Products, vif; D019409:Interleukin-15; D018449:SAIDS Vaccines; D019444:Vaccines, DNA; D007371:Interferon-gamma