Vaccination of macaques with long-standing SIVmac251 infection lowers the viral set point after cessation of antiretroviral therapy.
A cohort of rhesus macaques with long-standing SIVmac251 infection (> or =5 mo) was treated with continuous antiretroviral therapy (ART). A group of eight macaques was vaccinated with or without simultaneous administration of low dose IL-2 with the highly attenuated poxvirus vector (NYVAC) vaccine candidate expressing the SIVmac structural gag-pol-env (gpe) genes and a novel chimeric fusion protein derived from the rev-tat-nef (rtn) regulatory genes. Control groups consisted of mock-vaccinated macaques or animals treated only with IL-2. Vaccination significantly expanded both virus-specific CD4(+) and CD8(+) T cell responses, and IL-2 further increased the vaccine-induced response to an immunodominant Gag epitope. Following antiretroviral treatment interruption, the viral set point was significantly lower in vaccinated than in control macaques for at least 4 consecutive mo, and viral containment was inversely correlated with vaccine-induced, virus-specific CD4(+) and CD8(+) T cell responses. These data provide the proof of concept that therapeutic vaccination before cessation of ART may be a feasible approach in the clinical management of HIV-1 infection.
Tryniszewska
Elzbieta
E
Basic Research Laboratory, National Cancer Institute, Bethesda, MD 20892, USA.
Nacsa
Janos
J
Lewis
Mark G
MG
Silvera
Peter
P
Montefiori
David
D
Venzon
David
D
Hel
Zdenek
Z
Parks
Robyn Washington
RW
Moniuszko
Marcin
M
Tartaglia
Jim
J
Smith
Kendall A
KA
Franchini
Genoveffa
G
D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000821:virology; D004359:Drug Therapy, Combination; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D007115:Immunization Schedule; D007376:Interleukin-2 / Q000008:administration & dosage / Q000627:therapeutic use; D008253:Macaca mulatta; D018449:SAIDS Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000188:drug therapy / Q000276:immunology / Q000517:prevention & control* / Q000821:virology*; D015302:Simian Immunodeficiency Virus / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D014766:Viremia / Q000188:drug therapy / Q000276:immunology / Q000517:prevention & control; D014779:Virus Replication / Q000187:drug effects / Q000276:immunology*
D000998:Antiviral Agents; D018984:Epitopes, T-Lymphocyte; D007376:Interleukin-2; D018449:SAIDS Vaccines