title: Vaccination of macaques with long-standing SIVmac251 infection lowers the viral set point after cessation of antiretroviral therapy.
abstract: 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.
authors.affiliation: Basic Research Laboratory, National Cancer Institute, Bethesda, MD 20892, USA.
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Tryniszewska
authors.forename: Janos
authors.initials: J
authors.lastname: Nacsa
authors.forename: Mark G
authors.initials: MG
authors.lastname: Lewis
authors.forename: Peter
authors.initials: P
authors.lastname: Silvera
authors.forename: David
authors.initials: D
authors.lastname: Montefiori
authors.forename: David
authors.initials: D
authors.lastname: Venzon
authors.forename: Zdenek
authors.initials: Z
authors.lastname: Hel
authors.forename: Robyn Washington
authors.initials: RW
authors.lastname: Parks
authors.forename: Marcin
authors.initials: M
authors.lastname: Moniuszko
authors.forename: Jim
authors.initials: J
authors.lastname: Tartaglia
authors.forename: Kendall A
authors.initials: KA
authors.lastname: Smith
authors.forename: Genoveffa
authors.initials: G
authors.lastname: Franchini
mesh_terms: 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*
chemical_list: D000998:Antiviral Agents; D018984:Epitopes, T-Lymphocyte; D007376:Interleukin-2; D018449:SAIDS Vaccines