Development of a HIV-1 lipopeptide antigen pulsed therapeutic dendritic cell vaccine
| Autor: | Susan Burkeholder, Bryan King, Lee Roberts, Amanda Cobb, Derek Blankenship, Holly Mead, Monica Montes, Jacques Banchereau, Rajaram Ranganathan, Jennifer P Finholt, A. Carson Harrod, A. Karolina Palucka, L Sloan, Yves Levy |
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| Rok vydání: | 2010 |
| Předmět: |
Adult
HIV Antigens medicine.medical_treatment CD14 Immunology Molecular Sequence Data HIV Infections Biology Lymphocyte Activation Peripheral blood mononuclear cell Transplantation Autologous chemistry.chemical_compound Lipopeptides Antigen T-Lymphocyte Subsets Antiretroviral Therapy Highly Active medicine Immunology and Allergy Humans Amino Acid Sequence AIDS Vaccines Immunogenicity Lipopeptide Cell Differentiation Immunotherapy Dendritic cell Dendritic Cells Virology Combined Modality Therapy chemistry HIV-1 Cytokines Chemokines CD80 Epitope Mapping |
| Zdroj: | Journal of immunological methods. 365(1-2) |
| ISSN: | 1872-7905 |
| Popis: | 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). |
| Databáze: | OpenAIRE |
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