title: Development of a HIV-1 lipopeptide antigen pulsed therapeutic dendritic cell vaccine.
abstract: In the search for a therapeutic HIV-1 vaccine, we describe herein the development of a monocyte-derived dendritic cell (DC) vaccine loaded with a mixture of HIV-1-antigen lipopeptides (ANRS HIV-LIPO-5 Vaccine). LIPO-5 is comprised of five HIV-1-antigen peptides (Gag(17-35), Gag(253-284), Nef(66-97), Nef(116-145), and Pol(325-355)), each covalently linked to a palmitoyl-lysylamide moiety. Monocytes enriched from HIV-1-infected highly active antiretroviral therapy (HAART)-treated patients were cultured for three days with granulocyte-macrophage colony-stimulating factor and alpha-interferon. At day 2, the DCs were loaded with ANRS HIV-LIPO-5 vaccine, activated with lipopolysaccharide, harvested at day 3 and frozen. Flow cytometry analysis of thawed DC vaccines showed expression of DC differentiation markers: CD1b/c, CD14, HLA-DR, CD11c, co-stimulatory molecule CD80 and DC maturation marker CD83. DCs were capable of eliciting an HIV-1-antigen-specific response, as measured by expansion of autologous CD4(+) and CD8(+) T-cells. The expanded T-cells secreted gamma-IFN and interleukin (IL)-13, but not IL-10. The safety and immunogenicity of this DC vaccine are being evaluated in a Phase I/II clinical trial in chronically HIV-1-infected patients on HAART (clinicaltrials.gov identifier: NCT00796770).
authors.affiliation: Baylor Institute for Immunology Research, Dallas, TX, USA.
authors.forename: Amanda
authors.initials: A
authors.lastname: Cobb
authors.forename: Lee K
authors.initials: LK
authors.lastname: Roberts
authors.forename: A Karolina
authors.initials: AK
authors.lastname: Palucka
authors.forename: Holly
authors.initials: H
authors.lastname: Mead
authors.forename: Monica
authors.initials: M
authors.lastname: Montes
authors.forename: Rajaram
authors.initials: R
authors.lastname: Ranganathan
authors.forename: Susan
authors.initials: S
authors.lastname: Burkeholder
authors.forename: Jennifer P
authors.initials: JP
authors.lastname: Finholt
authors.forename: Derek
authors.initials: D
authors.lastname: Blankenship
authors.forename: Bryan
authors.initials: B
authors.lastname: King
authors.forename: Louis
authors.initials: L
authors.lastname: Sloan
authors.forename: A Carson
authors.initials: AC
authors.lastname: Harrod
authors.forename: Yves
authors.initials: Y
authors.lastname: Lévy
authors.forename: Jacques
authors.initials: J
authors.lastname: Banchereau
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000627:therapeutic use*; D000328:Adult; D000595:Amino Acid Sequence; D023241:Antiretroviral Therapy, Highly Active; D002454:Cell Differentiation; D018925:Chemokines / Q000096:biosynthesis; D003131:Combined Modality Therapy; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000637:transplantation; D018604:Epitope Mapping; D015488:HIV Antigens / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology / Q000628:therapy*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D055666:Lipopeptides / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014182:Transplantation, Autologous
chemical_list: D016915:AIDS Vaccines; D018925:Chemokines; D016207:Cytokines; D015488:HIV Antigens; D055666:Lipopeptides