Recombinant live vaccine candidates against tuberculosis

Tuberculosis (TB) remains among the most deadly health threats to humankind despite availability of several potent antibiotics and a vaccine, bacille Calmette-Guérin (BCG). BCG partially protects children but not adults from the disease. Growing knowledge of the molecular basis of infection, immunity, and pathology in TB has driven various approaches, which strive to complement or replace BCG with more effective vaccines. Three recombinant live TB vaccine candidates have entered clinical trials. These candidates have been genetically engineered to be attenuated, to overexpress TB antigens and/or to secrete bacterial perforins, ultimately seeking to trigger a robust immune response thereby providing long-lasting protection against TB.

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► A robust pipeline of recombinant live TB vaccines aims to replace BCG.
► Current candidates are better than BCG in controlling TB in preclinical models.
► Three candidates in clinical trials signal hope for medium-term market introduction.
► Candidates do not prevent or eradicate infection.
► BCG can serve as vaccine platform to address the needs of diseases other than TB.