Disruption of the SapM locus in Mycobacterium bovis BCG improves its protective efficacy as a vaccine against M. tuberculosis.
Bottom Line: Both systemic and intratracheal challenge of mice with Mycobacterium tuberculosis following vaccination showed that the SapM mutant, compared to the parental BCG vaccine, provided better protection: it led to longer-term survival.Persistence of the SapM-mutated BCG in vivo resembled that of the parental BCG indicating that this mutation will likely not compromise the safety of the BCG vaccine.The SapM mutant BCG vaccine was more effective than the parental vaccine in inducing recruitment and activation of CD11c(+) MHC-II(int) CD40(int) dendritic cells (DCs) to the draining lymph nodes.
Affiliation: Unit for Medical Biotechnology, Department for Molecular Biomedical Research, Ghent, Belgium. email@example.comShow MeSH
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Mentions: To evaluate the safety of the mutant BCG strains, we tested them for parameters related to chronic mycobacterial infection. To analyse bacterial persistence in vivo, BALB/c mice were infected intravenously with M. bovis BCG or M. bovis BCG mutants (Mb2203, Mb1661c or SapM). The bacterial load in the lungs and spleen was determined 2, 4, and 12 weeks post-infection. Two weeks after infection, the load of the parental strain in the lung was slightly higher than the loads of the mutants. Four weeks post-infection, the mutants reached similar numbers of CFU in the lungs and spleen as the WT M. bovis BCG (Fig 2A and B, Suppl. Fig 2A and B). Overall, bacterial numbers in lung and spleen decreased over time, indicating partial clearance.
Affiliation: Unit for Medical Biotechnology, Department for Molecular Biomedical Research, Ghent, Belgium. firstname.lastname@example.org