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Abstract
A safer and more effective anti-Tuberculosis vaccine is still an urgent need. We probed the effects of monosodium urate crystals (MSU) on innate immunity to improve the Bacille Calmette-Guerin (BCG) vaccination. Results showed that in vitro MSU cause an enduring macrophage stimulation of the anti-mycobacterial response, measured as intracellular killing, ROS production and phagolysosome maturation. The contribution of MSU to anti-mycobacterial activity was also shown in vivo. Mice vaccinated in the presence of MSU showed a lower number of BCG in lymph nodes draining the vaccine inoculation site, in comparison to mice vaccinated without MSU. Lastly, we showed that MSU improved the efficacy of BCG vaccination in mice infected with Mycobacterium tuberculosis (MTB), measured in terms of lung and spleen MTB burden. These results demonstrate that the use of MSU as adjuvant may represent a novel strategy to enhance the efficacy of BCG vaccination.
Highlights
The most recent report from WHO estimates 8.8 million new incident Tuberculosis (TB) cases worldwide and 1.3 million deaths [1], making TB one of the most deadly human infectious disease
The present study reports evidences showing the capability of monosodium urate crystals (MSU) to induce in vitro a persisting innate anti-mycobacterial activation, which was associated in vivo with a better efficacy of Bacille Calmette-Guerin (BCG) vaccination
DTHP-1 cells infected with BCG at the MOI of 1 were stimulated with MSU and intracellular mycobacterial viability was evaluated by colony forming unit (CFU) assay
Summary
The most recent report from WHO estimates 8.8 million new incident Tuberculosis (TB) cases worldwide and 1.3 million deaths [1], making TB one of the most deadly human infectious disease. The fact that high proportions of HIV infected individuals live in TB endemic regions poses a significant risk when it comes to BCG (or other live) vaccine, given that the majority of serious complications following BCG administration occur in immunocompromised patients [3]. In this context, the generation of a safer and more efficacious BCG-based anti-TB vaccine may require the association of BCG with novel.
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