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Mary A. Marovich, John R. Mascola, Michael A. Eller, Mark K. Louder, Pierre A. Caudrelier, Raphaelle El-Habib, Silvia Ratto-Kim, Josephine H. Cox, Jeffrey R. Currier, Bruce L. Levine, Carl H. June, Wendy B. Bernstein, Merlin L. Robb, Beatrice Schuler-Thurner, Ralph M. Steinman, Deborah L. Birx, Sarah Schlesinger-Frankel, Preparation of Clinical-Grade Recombinant Canarypox–Human Immunodeficiency Virus Vaccine–Loaded Human Dendritic Cells, The Journal of Infectious Diseases, Volume 186, Issue 9, 1 November 2002, Pages 1242–1252, https://doi.org/10.1086/344302
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Abstract
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