TY - JOUR
T1 - Development of a HIV-1 lipopeptide antigen pulsed therapeutic dendritic cell vaccine
AU - Cobb, Amanda
AU - Roberts, Lee K.
AU - Palucka, A. Karolina
AU - Mead, Holly
AU - Montes, Monica
AU - Ranganathan, Rajaram
AU - Burkeholder, Susan
AU - Finholt, Jennifer P.
AU - Blankenship, Derek
AU - King, Bryan
AU - Sloan, Louis
AU - Harrod, A. Carson
AU - Lévy, Yves
AU - Banchereau, Jacques
N1 - Funding Information:
We thank the volunteers for participation in this study. We thank the medical staff from North Texas Infectious Diseases Consultants. We thank Dr. M. Ramsay and C. Samuelsen for continuous support. A.K.P. holds the Ramsay Chair for Cancer Immunology. We thank Eynav Klechevsky for technical discussions. The development of this DC vaccine was supported by the French National Agency for AIDS Research (ANRS) Paris, France and by grants from BHCS Foundation. Author contribution: A.C. designed and performed the research, analyzed results, made the figures and wrote the manuscript; H.M., M.M., R.R., S.B., and J.P.F contributed technical assistance, D.B. contributed statistical analysis, A.C.H. contributed regulatory and administrative assistance, B.K. and L.S. provided HIV-1 samples for research, Y.L., A.K.P., L.K.R. and J.B designed the research and wrote the manuscript.
PY - 2011/2/28
Y1 - 2011/2/28
N2 - 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).
AB - 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).
KW - ANRS-LIPO-5 vaccine
KW - Antigen-specific T-cells
KW - DC
KW - HIV
KW - IFN-γ
KW - Vaccine development
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U2 - 10.1016/j.jim.2010.11.002
DO - 10.1016/j.jim.2010.11.002
M3 - Article
C2 - 21093448
AN - SCOPUS:79551582028
SN - 0022-1759
VL - 365
SP - 27
EP - 37
JO - Journal of Immunological Methods
JF - Journal of Immunological Methods
IS - 1-2
ER -