TY - JOUR
T1 - Preparation of clinical-grade recombinant canarypox-human immunodeficiency virus vaccine-loaded human dendritic cells
AU - Marovich, Mary A.
AU - Mascola, John R.
AU - Eller, Michael A.
AU - Louder, Mark K.
AU - Caudrelier, Pierre A.
AU - El-Habib, Raphaelle
AU - Ratto-Kim, Silvia
AU - Cox, Josephine H.
AU - Currier, Jeffrey R.
AU - Levine, Bruce L.
AU - June, Carl H.
AU - Bernstein, Wendy B.
AU - Robb, Merlin L.
AU - Schuler-Thurner, Beatrice
AU - Steinman, Ralph M.
AU - Birx, Deborah L.
AU - Schlesinger-Frankel, Sarah
N1 - Funding Information:
1Division of Retrovirology, US Military HIV Research Program, Rockville, and 2Vaccine Research Center, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland; 3Abramson Family Cancer Research Institute, University of Pennsylvania Cancer Center, Philadelphia; 4Rockefeller University, New York, New York; 5IDM Biotech, Montreal, Canada; 6Aventis Pasteur, Lyon, France; 7University Hospital of Erlangen, Erlangen, Germany
PY - 2002/11/1
Y1 - 2002/11/1
N2 - Preclinical data are reported that support a human immunodeficiency virus (HIV) vaccine strategy using recombinant canarypox-HIV vectors (ALVAC-HIV) to load human dendritic cells (DCs) with HIV antigens. Clinical-grade DCs were infected with good manufacturing practice-grade ALVAC-HIV vaccine constructs. ALVAC infection, HIV gene expression, and DC viability and function were monitored by use of immunohistochemistry, flow cytometry, blastogenesis assays, antigen-specific interferon (IFN)-γ enzyme-linked immunospot assay, and enzyme-linked immunosorbent assay protein detection. The vaccines infected both immature and mature DCs, and intracellular HIV-1 Gag protein was detected within hours. ALVAC-HIV induced DC maturation that was mediated by tumor necrosis factor-α and induced DC apoptosis that was directly related to the length of vaccine exposure. Of importance, the infected DCs remained functional in T cell stimulation assays and induced HIV antigen-specific CD8+ T cell production of IFN-γ from cells of HIV-1-infected individuals. These data support an ongoing HIV vaccine trial comparing conventional vaccine delivery routes with ex vivo vaccine-loaded autologous DCs for immunogenicity in HIV-1-uninfected volunteers.
AB - Preclinical data are reported that support a human immunodeficiency virus (HIV) vaccine strategy using recombinant canarypox-HIV vectors (ALVAC-HIV) to load human dendritic cells (DCs) with HIV antigens. Clinical-grade DCs were infected with good manufacturing practice-grade ALVAC-HIV vaccine constructs. ALVAC infection, HIV gene expression, and DC viability and function were monitored by use of immunohistochemistry, flow cytometry, blastogenesis assays, antigen-specific interferon (IFN)-γ enzyme-linked immunospot assay, and enzyme-linked immunosorbent assay protein detection. The vaccines infected both immature and mature DCs, and intracellular HIV-1 Gag protein was detected within hours. ALVAC-HIV induced DC maturation that was mediated by tumor necrosis factor-α and induced DC apoptosis that was directly related to the length of vaccine exposure. Of importance, the infected DCs remained functional in T cell stimulation assays and induced HIV antigen-specific CD8+ T cell production of IFN-γ from cells of HIV-1-infected individuals. These data support an ongoing HIV vaccine trial comparing conventional vaccine delivery routes with ex vivo vaccine-loaded autologous DCs for immunogenicity in HIV-1-uninfected volunteers.
UR - http://www.scopus.com/inward/record.url?scp=0036839319&partnerID=8YFLogxK
U2 - 10.1086/344302
DO - 10.1086/344302
M3 - Article
C2 - 12402193
AN - SCOPUS:0036839319
SN - 0022-1899
VL - 186
SP - 1242
EP - 1252
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 9
ER -