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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