Preparation of clinical-grade recombinant canarypox-human immunodeficiency virus vaccine-loaded human dendritic cells

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

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27 Scopus citations


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.

Original languageEnglish
Pages (from-to)1242-1252
Number of pages11
JournalJournal of Infectious Diseases
Issue number9
StatePublished - 1 Nov 2002
Externally publishedYes


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