Mycobacterium bovis Dmce2 double deletion mutant protects cattle against challenge with virulent M. bovis

A Mycobacterium bovis strain deleted in mce2A and mce2B genes (M. bovis Δmce2) was tested as an experimental vaccine in cattle challenged with a virulent M. bovis strain. Three-and-a-half-month old calves (n = 5 to 6 per group) were vaccinated and challenged with a virulent strain of M. bovis by the intratracheal route 9 weeks after vaccination. A non-vaccinated group and a group vaccinated with BCG were included as controls. Blood samples were collected to measure IFN-γ by an interferon-gamma release assay (IGRA), cytometry and cytokine responses of bovine purified protein derivative (PPD) restimulated peripheral blood mononuclear cells (PBMCs). The IGRA test showed IFN-γ values similar to pre-vaccination except for the animals vaccinated with M. bovis Δmce2, where a significant increase was observed at 30 days post-vaccination. The expression of IL-2R on CD4+ cells in response to PPD from the animals vaccinated with Δmce2 increased at 15 days post-vaccination compared to cells from non-vaccinated group. Vaccination of cattle with M. bovis Δmce2 induced the highest (P < 0.05) expression of IFN-γ and IL-17 mRNA upon PPD stimulation of PBMCs compared to vaccination with BCG or that for the non-vaccinated group. There was a weak positive correlation between the production of these proinflammatory cytokines post-vaccination and reduced pathology scores post-challenge. The animals were euthanized and necropsied 100 days after challenge. The group vaccinated with M. bovis Δmce2 displayed a significantly lower histopathological score for lesions in lungs and pulmonary lymph nodes than for the other groups (P < 0.05). A marked positive reaction to tuberculin intradermal test was observed post-vaccination in animals vaccinated with M. bovis Δmce2 compared to those vaccinated with BCG or the non-vaccinated group. In contrast, after challenge, non-vaccinated animals had greater skin test responses than the vaccinated animals. In summary, M. bovis Δmce2 is a promising vaccine candidate to control M. bovis pathogenesis in cattle.

Bibliographic Details

Main Authors:	Blanco, Federico Carlos, Bianco, María Veronica, Garbaccio, Sergio Gabriel, Meikle, Virginia, Gravisaco, María José, Montenegro, Valeria Noely, Alfonseca, Edgar, Singh, Mahavir G., Barandiaran, Soledad, Canal, Ana María, Vagnoni, Lucas Emilio, Buddle, Bryce Malcom, Bigi, Fabiana, Cataldi, Angel Adrian
Format:	info:ar-repo/semantics/artículo biblioteca
Language:	eng
Published:	Elsevier 2013-05
Subjects:	Tuberculosis, Infección por Mycobacterium bovis, Vacuna Viva, Ganado Bovino, Organismos Patógenos Virulentos, Mycobacterium bovis Infections, Live Vaccines, Cattle, Virulent Pathogens,
Online Access:	http://hdl.handle.net/20.500.12123/8172 https://www.sciencedirect.com/science/article/abs/pii/S1472979213000127 https://doi.org/10.1016/j.tube.2013.02.004
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