Tuberculosis remains a major global health threat. Although morethan 3 billion doses of the BCG vaccine have been administered to fighttuberculosis, the ability of the BCG vaccine to protect adults is verylimited, as is its efficacy against newly emerging isolates.
In a study appearing online on August 18 in advance of print publication of the September 1 issue of the Journal of Clinical Investigation,Stefan Kaufmann and colleagues from the Max Planck Institute devise astrategy to boost the immunogenicity of BCG and describe a novelvaccine strain with high efficacy against tuberculosis. The researchersengineer a BCG strain that secretes the listeriolysin protein, whichpunches holes in the membranes of phagosomes where M. tuberculosis islocated, allowing better T cell-mediated immunity. Becauselisteriolysin works optimally at a pH of 5.8, the researchers alsodeleted the urease C gene of BCG, which normally plays a role in pHneutralization of the phagosome. The lack of urease C allows phagosomalacidification and provides an ideal pH environment for listeriolysin.
The new BCG vaccine strain protects mice against tuberculosissignificantly better than the parental BCG. Superior protection is notonly induced against the laboratory strain of M. tuberculosis but alsoagainst a clinical isolate of the Beijing/W family, a straing oftuberculosis that is spreading all over the world, is drug-resistant,and is responsible for the most threatening disease outbreaks.
TITLE: Increased vaccine efficacy against tuberculosis ofrecombinant Mycobacterium bovis bacille Calmette-Guérin mutants thatsecrete listeriolysin
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