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 a strategy to boost the immunogenicity of BCG and describe a novel vaccine strain with high efficacy against tuberculosis. The researchers engineer a BCG strain that secretes the listeriolysin protein, which punches holes in the membranes of phagosomes where M. tuberculosis is located, allowing better T cell-mediated immunity. Because listeriolysin works optimally at a pH of 5.8, the researchers also deleted the urease C gene of BCG, which normally plays a role in pH neutralization of the phagosome. The lack of urease C allows phagosomal acidification and provides an ideal pH environment for listeriolysin.
The new BCG vaccine strain protects mice against tuberculosis significantly better than the parental BCG. Superior protection is not only induced against the laboratory strain of M. tuberculosis but also against a clinical isolate of the Beijing/W family, a straing of tuberculosis that is spreading all over the world, is drug-resistant, and is responsible for the most threatening disease outbreaks.