title: Control of viremia and prevention of AIDS following immunotherapy of SIV-infected macaques with peptide-pulsed blood.
abstract: Effective immunotherapies for HIV are needed. Drug therapies are life-long with significant toxicities. Dendritic-cell based immunotherapy approaches are promising but impractical for widespread use. A simple immunotherapy, reinfusing fresh autologous blood cells exposed to overlapping SIV peptides for 1 hour ex vivo, was assessed for the control of SIV(mac251) replication in 36 pigtail macaques. An initial set of four immunizations was administered under antiretroviral cover and a booster set of three immunizations administered 6 months later. Vaccinated animals were randomized to receive Gag peptides alone or peptides spanning all nine SIV proteins. High-level, SIV-specific CD4 and CD8 T-cell immunity was induced following immunization, both during antiretroviral cover and without. Virus levels were durably approximately 10-fold lower for 1 year in immunized animals compared to controls, and a significant delay in AIDS-related mortality resulted. Broader immunity resulted following immunizations with peptides spanning all nine SIV proteins, but the responses to Gag were weaker in comparison to animals only immunized with Gag. No difference in viral outcome occurred in animals immunized with all SIV proteins compared to animals immunized against Gag alone. Peptide-pulsed blood cells are an immunogenic and effective immunotherapy in SIV-infected macaques. Our results suggest Gag alone is an effective antigen for T-cell immunotherapy. Fresh blood cells pulsed with overlapping Gag peptides is proceeding into trials in HIV-infected humans.
authors.affiliation: Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Robert
authors.initials: R
authors.lastname: De Rose
authors.forename: Caroline S
authors.initials: CS
authors.lastname: Fernandez
authors.forename: Miranda Z
authors.initials: MZ
authors.lastname: Smith
authors.forename: C Jane
authors.initials: CJ
authors.lastname: Batten
authors.forename: Sheilajen
authors.initials: S
authors.lastname: Alcântara
authors.forename: Vivienne
authors.initials: V
authors.lastname: Peut
authors.forename: Erik
authors.initials: E
authors.lastname: Rollman
authors.forename: Liyen
authors.initials: L
authors.lastname: Loh
authors.forename: Rosemarie D
authors.initials: RD
authors.lastname: Mason
authors.forename: Kim
authors.initials: K
authors.lastname: Wilson
authors.forename: Matthew G
authors.initials: MG
authors.lastname: Law
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Handley
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Kent
mesh_terms: D000818:Animals; D016913:Blood Component Transfusion; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D015683:Gene Products, gag / Q000008:administration & dosage* / Q000276:immunology; D007167:Immunotherapy / Q000379:methods*; D008136:Longevity; D008254:Macaca nemestrina; D008297:Male; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control*; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D014766:Viremia / Q000628:therapy*
chemical_list: D015683:Gene Products, gag