An Escherichia coli-based oral vaccine against urinary tract infections potently activates human dendritic cells.
OBJECTIVE
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.
D000276:Adjuvants, Immunologic / Q000494:pharmacology* / Q000627:therapeutic use; D015703:Antigens, CD / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D004926:Escherichia coli / Q000276:immunology; D004927:Escherichia coli Infections / Q000276:immunology / Q000517:prevention & control; D022361:Escherichia coli Vaccines / Q000494:pharmacology* / Q000627:therapeutic use; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D009000:Monocytes / Q000276:immunology; D014552:Urinary Tract Infections / Q000276:immunology / Q000517:prevention & control
D000276:Adjuvants, Immunologic; D015703:Antigens, CD; D022361:Escherichia coli Vaccines; D007371:Interferon-gamma