Development of a HIV-1 lipopeptide antigen pulsed therapeutic dendritic cell vaccine

Amanda Cobb, Lee K. Roberts, A. Karolina Palucka, Holly Mead, Monica Montes, Rajaram Ranganathan, Susan Burkeholder, Jennifer P. Finholt, Derek Blankenship, Bryan King, Louis Sloan, A. Carson Harrod, Yves Lévy, Jacques Banchereau

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

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 (Gag17-35, Gag253-284, Nef66-97, Nef116-145, and Pol325-355), 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).

Original languageEnglish (US)
Pages (from-to)27-37
Number of pages11
JournalJournal of Immunological Methods
Volume365
Issue number1-2
DOIs
StatePublished - Feb 28 2011
Externally publishedYes

Keywords

  • ANRS-LIPO-5 vaccine
  • Antigen-specific T-cells
  • DC
  • HIV
  • IFN-γ
  • Vaccine development

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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