Tuberculosis (TB) is the world’s leading infectious cause of death. It is estimated that about a third of the world’s population are infected with Mycobacterium tuberculosis (Mtb). Despite significant advances in reducing mortality in recent decades through improved diagnosis and drug treatment regimens, TB still causes enormous human suffering, a major economic burden and is one of the major drivers of global inequity. Whilst neonatal BCG vaccination is partially efficacious at protecting infants and young children against severe forms of TB, it is poorly protective against pulmonary disease in adolescents and adults, and therefore ineffective at reducing Mtb transmission. Reaching the WHO End TB Strategy targets of a 95% reduction in TB mortality and a 90% reduction in TB incidence, worldwide, by 2035, will require a new vaccine that is effective at preventing adult tuberculosis. Vaccines also offer the best chance to contain the accelerating spread of multi-drug resistant tuberculosis.