An Escherichia coli-based oral vaccine against urinary tract infections potently activates human dendritic cells

• Published in: Urology (Ridgewood, N.J.) Vol. 60; no. 3; pp. 521 - 526
• Main Authors: Schmidhammer, Silvia, Ramoner, Reinhold, Höltl, Lorenz, Bartsch, Georg, Thurnher, Martin, Zelle-Rieser, Claudia
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.09.2002; Elsevier Science
• Subjects: Adjuvants, Immunologic - pharmacology; Adjuvants, Immunologic - therapeutic use; Antigens, CD - immunology; Biological and medical sciences; Cells, Cultured; Dendritic Cells - drug effects; Dendritic Cells - immunology; Dose-Response Relationship, Immunologic; Epidemiology. Vaccinations; Escherichia coli - immunology; Escherichia coli Infections - immunology; Escherichia coli Infections - prevention & control; Escherichia coli Vaccines - pharmacology; Escherichia coli Vaccines - therapeutic use; Flow Cytometry; General aspects; Humans; Immunophenotyping; Infectious diseases; Interferon-gamma - immunology; Lymphocyte Culture Test, Mixed; Medical sciences; Monocytes - immunology; Urinary Tract Infections - immunology; Urinary Tract Infections - prevention & control; Human; Dendritic cell; Relapse; Urinary system disease; Escherichia coli; Vaccination; Oral administration; Urinary tract disease; Urinary tract; Infection; Antigen; Prevention; Bacteriosis; Bacteria; Enterobacteriaceae; Immune system
• ISSN: 0090-4295; 1527-9995
• DOI: 10.1016/S0090-4295(02)01767-3

Objectives. To investigate the effects of Uro-Vaxom, an oral vaccine against Escherichia coli urinary tract infections, on human monocyte-derived dendritic cells (moDCs). Dendritic cells (DCs) are important antigen-presenting cells of the immune system. DCs are considered promising cellular adjuvants for inducing immunity against cancer or infectious diseases. Methods. moDCs were generated in the presence of granulocyte-macrophage colony-stimulating factor and interleukin-4. Flow cytometric phenotyping, as well as the ability to stimulate T cells in an allogeneic mixed leukocyte reaction, was used to assess the effects of Uro-Vaxom on human moDCs. In addition, interferon-gamma and interleukin-4 production by T cells stimulated with Uro-Vaxom-activated moDCs were measured by intracellular fluorescence-activated cell sorter-staining at the single-cell level. Results. Uro-Vaxom induced the terminal maturation of CD83+ moDCs in a dose-dependent manner. Phenotypic analyses revealed that Uro-Vaxom-activated moDCs displayed a phenotype of mature DCs with high levels of MHC molecules and increased levels of co-stimulatory molecules (CD80, CD86). Consistent with these findings, Uro-Vaxom-activated moDCs potently stimulated T-cell proliferation and interferon-gamma production in the allogeneic mixed leukocyte reaction. Conclusions. In DC-based immunotherapy, Uro-Vaxom could be used as a stimulant of DC maturation, which meets the standards of good manufacturing practice. In future preclinical studies, we will evaluate the effectiveness of a vaccination with Uro-Vaxom-activated moDCs. It could be an attractive treatment option in preventing recurrent E. coli urinary tract infections in predisposed individuals.