A Therapeutic SIV DNA Vaccine Elicits T-Cell Immune Responses,but No Sustained Control of Viremia in SIVmac239-Infected Rhesus Macaques

Abstract

The immunologic and virologic outcome of therapeutic DNA-vaccines administered during antiretroviral therapy (ART) using electroporation with or without (interleukin) IL-2 treatment was evaluated in the SIVmac239/macaque model. Rhesus macaques inoculated with pathogenic SIVmac239 were treated with ART [(R(-9-(2-phosphonomethoxypropyl) adenine) (PMPA), FTC, Zerit^®] from weeks 13 to 41 postinfection (wpi). Group 1 (n = 7) received ART only, groups 2 and 3 (each n = 6) additionally received SIVmac239-derived gp140Env, GagPol, and TatRevNef plasmids by in vivo electroporation at 22, 26, 30, and 34 wpi, and group 3 also IL-2 for 14 days after each vaccination. Endpoints evaluated were viral load, Gag_181–189-specific CD8⁺ T-cell responses in MamuA01⁺ animals, lymphoproliferative responses, and CD4 T-cell counts. Viremia in all animals dropped below 200 RNA copies/ml during ART. Frequencies of Gag_181–189-specific CD8⁺ T cells prior to ART were detectable in all three groups (1.27–3.01%) and increased significantly (p < 0.01) postvaccination with maximum responses after the fourth immunization (0.2% versus 3.49–7.15%). Gag_181–189-specific CD8⁺ T-cell frequencies increased post-ART cessation in all groups and remained at significantly higher levels (p < 0.001) until the end of the study (75 wpi) in both groups of vaccinated animals. Lymphoproliferative responses were detected against Gag in a limited number of animals after vaccination and post-ART. However, plasma RNA viral loads rebounded after ART termination to similar levels in all three groups, but remained below 10⁵ copies/ml until the end of the study, which could be a late effect of the triple drug therapy.