Preparation of Clinical‐Grade Recombinant Canarypox–Human Immunodeficiency Virus Vaccine–Loaded Human Dendritic Cells
| Autor: | John R. Mascola, Josephine H. Cox, Merlin L. Robb, Pierre A. Caudrelier, Raphaelle El-Habib, Silvia Ratto-Kim, Beatrice Schuler-Thurner, Wendy B. Bernstein, Jeffrey R. Currier, Michael A. Eller, Mark K. Louder, Deborah L. Birx, Ralph M. Steinman, Bruce L. Levine, Carl H. June, Sarah Schlesinger-Frankel, Mary A. Marovich |
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| Rok vydání: | 2002 |
| Předmět: |
Canarypox
T-Lymphocytes T cell Gene Products gag Cell Separation Canarypox virus Lymphocyte Activation Immunophenotyping Antigens CD Interferon medicine Humans Immunology and Allergy Cytotoxic T cell AIDS Vaccines Vaccines Synthetic biology virus diseases Viral Vaccines Dendritic Cells Dendritic cell biology.organism_classification Virology Vaccination Infectious Diseases HIV Antigens medicine.anatomical_structure Immunology medicine.drug |
| Zdroj: | The Journal of Infectious Diseases. 186:1242-1252 |
| ISSN: | 1537-6613 0022-1899 |
| DOI: | 10.1086/344302 |
| Popis: | 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)-gamma 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-alpha 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-gamma 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. |
| Databáze: | OpenAIRE |
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