Grant: Project Grant

Ever since German scientist Robert Koch first discovered Mycobacterium tuberculosis (Mtb) to be the infectious agent of tuberculosis in 1882, it has defied efforts by scientists to prevent or cure the disease. The presence of Mtb DNA in ancient Egyptian mummies (dated 1550-1080 BC) suggests a long-standing evolutionary relationship between this bacterium and humans. Despite the world-wide application of BCG vaccination and other anti-Mtb interventions, Mtb remains one of the deadliest human pathogens killing annually two million people. Eight to ten million new cases of active tuberculosis occur each year due in large part to asymptomatic people chronically infected with Mtb. The ability of Mtb to persist in individuals with apparently normal immune systems implies that Mtb has developed strategies to avoid, evade, and even subvert our host defense system. Considering BCG is the only available vaccine for preventing the disseminated form of TB in children but not adults, understanding the protective mechanisms of BCG in children can map out the critical cellular and molecular immune pathways of protection against TB. Thus, the major objective of this proposal is to identify correlates of immune protection and potentially prolong their anti-TB capacity for the development of a novel TB vaccine.