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Vaccination with a BCG strain overexpressing Ag85B protects cattle against Mycobacterium bovis challenge

Colaborador(es): Rizzi, C | Bianco, María Verónica | Blanco, Federico C | Soria, Marcelo Abel | Gravisaco, María José | Montenegro, V | Vagnoni, Lucas | Buddle, B | Garbaccio, Sergio | Delgado, F | Leal, K. S | Cataldi, Angel Adrián | Dellagostin, O. A | Bigi, Fabiana.
ISSN: 1932-6203.Tipo de material: Artículos y capítulos. Recurso electrónico.Tema(s): BCG 85B VACCINE | BCG VACCINE | INTERLEUKIN 17 | INTERLEUKIN 4 | LEUCINE | UNCLASSIFIED DRUG | ANIMAL EXPERIMENT | ANIMAL MODEL | BACTERIAL STRAIN | BCG VACCINATION | BOVINE TUBERCULOSIS | CD4+ T LYMPHOCYTE | CD8+ T LYMPHOCYTE | CLINICAL EFFECTIVENESS | CONTROLLED STUDY | CYTOKINE PRODUCTION | CYTOKINE RESPONSE | DISEASE SEVERITY | GENE OVEREXPRESSION | GENETIC COMPLEMENTATION | INFECTION CONTROL | INFECTION PREVENTION | MYCOBACTERIUM BOVIS | NONHUMAN | PERIPHERAL BLOOD MONONUCLEAR CELL | PROTEIN EXPRESSION | PROTEIN PURIFICATION | WILD TYPE | ANIMALS | BCG VACCINE | CATTLE | CATTLE DISEASES | DNA PRIMERS | FLOW CYTOMETRY | INTERFERON-GAMMA | MYCOBACTERIUM BOVIS | POLYMERASE CHAIN REACTION | TUBERCULIN TEST | TUBERCULOSIS, BOVINE | Recursos en línea: Haga clic para acceso en línea | LINK AL EDITOR. En: PLoS ONE vol.7, no.12 (2012), p.e51396-Resumen: Mycobacterium bovis is the causative agent of tuberculosis in cattle but also infects other animals, including humans. Previous studies in cattle have demonstrated that the protection induced by BCG is not complete. In order to improve the protection efficacy of BCG, in this study we overexpressed Ag85B in a BCG Pasteur strain, by using an expression system based on the use of an auxotrophic strain for the leucine amino acid, and complementation with leuD. We found that vaccination of cattle with BCG overexpressing Ag85B induced higher production of IL-17 and IL-4 mRNA upon purified protein derivative [PPDB] stimulation of peripheral blood mononuclear cells [PBMCs] than vaccination with BCG. Moreover, the IL-17 mRNA expression after vaccination negatively correlated with disease severity resulting from a subsequent challenge with M. bovis, suggesting that this cytokine is a potential biomarker of cattle protection against bovine tuberculosis. Importantly, vaccination with the recombinant BCG vaccine protected cattle better than the wild-type BCG Pasteur.
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Mycobacterium bovis is the causative agent of tuberculosis in cattle but also infects other animals, including humans. Previous studies in cattle have demonstrated that the protection induced by BCG is not complete. In order to improve the protection efficacy of BCG, in this study we overexpressed Ag85B in a BCG Pasteur strain, by using an expression system based on the use of an auxotrophic strain for the leucine amino acid, and complementation with leuD. We found that vaccination of cattle with BCG overexpressing Ag85B induced higher production of IL-17 and IL-4 mRNA upon purified protein derivative [PPDB] stimulation of peripheral blood mononuclear cells [PBMCs] than vaccination with BCG. Moreover, the IL-17 mRNA expression after vaccination negatively correlated with disease severity resulting from a subsequent challenge with M. bovis, suggesting that this cytokine is a potential biomarker of cattle protection against bovine tuberculosis. Importantly, vaccination with the recombinant BCG vaccine protected cattle better than the wild-type BCG Pasteur.

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