Dietary pyridoxine controls efficacy of vitamin B6-auxotrophic tuberculosis vaccine bacillus Calmette-Guerin ΔureC::hly Δpdx1 in mice.

ABSTRACT:

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The only tuberculosis (TB) vaccine in use today, bacillus Calmette-Guérin (BCG), provides insufficient protection and can cause adverse events in immunocompromised individuals, such as BCGosis in HIV(+) newborns. We previously reported improved preclinical efficacy and safety of the recombinant vaccine candidate BCG ΔureC::hly, which secretes the pore-forming listeriolysin O of Listeria monocytogenes. Here, we evaluate a second-generation construct, BCG ΔureC::hly Δpdx1, which is deficient in pyridoxine synthase, an enzyme that is required for biosynthesis of the essential cofactor vitamin B6. This candidate was auxotrophic for vitamin B6 in a concentration-dependent manner, as was its survival in vivo. BCG ΔureC::hly Δpdx1 showed markedly restricted dissemination in sub

SUBMITTER: Gengenbacher M 

PROVIDER: S-EPMC4049106 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature