A therapeutic SIV DNA vaccine elicits T-cell immune responses, but no sustained control of viremia in SIVmac239-infected rhesus macaques.
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(181189)-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(181189)-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(181189)-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 10(5) copies/ml until the end of the study, which could be a late effect of the triple drug therapy.
zur Megede
Jan
J
Novartis Vaccines & Diagnostics Inc., Emeryville, California, USA.
Sanders-Beer
Brigitte
B
Silvera
Peter
P
Golightly
Dawn
D
Bowlsbey
Abigail
A
Hebblewaite
Diane
D
Sites
Deborah
D
Nieves-Duran
Lourdes
L
Srivastava
Ranjana
R
Otten
Gillis R
GR
Rabussay
Dietmar
D
Zhang
Lei
L
Ulmer
Jeffrey B
JB
Barnett
Susan W
SW
Donnelly
John J
JJ
D000818:Animals; D044966:Anti-Retroviral Agents / Q000008:administration & dosage*; D018791:CD4 Lymphocyte Count; D003131:Combined Modality Therapy; D004334:Drug Administration Schedule; D053672:Electrochemotherapy; D007155:Immunologic Factors / Q000627:therapeutic use; D007376:Interleukin-2 / Q000627:therapeutic use; D008253:Macaca mulatta; D018449:SAIDS Vaccines / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000188:drug therapy / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000821:virology; D019444:Vaccines, DNA / Q000276:immunology; D019562:Viral Load; D014766:Viremia / Q000188:drug therapy / Q000276:immunology*
D044966:Anti-Retroviral Agents; D007155:Immunologic Factors; D007376:Interleukin-2; D018449:SAIDS Vaccines; D019444:Vaccines, DNA