The history of vaccination against tuberculosis abounds with instances of scientific discovery and rediscovery. At the end of the 19th and beginning of the 20th century, following Robert Koch's announcement of his discovery of Mycobacterium tuberculosis in 1882, scientists across the world, including Koch himself, set out to invent a vaccine against tuberculosis. In 1908 Leon Calmette, a bacteriologist, and Camille Guérin, a veterinarian at the Pasteur Institute, Lille began an experiment to devise a vaccine by attenuating a Mycobacterium bovis strain until it lost its virulence. Thirteen years and 230 passages later, they were able to show that the strain was protective in animal models and no longer caused disease which was subsequently discovered to be primarily due to the loss of the genes in the region of difference 1 (RD1) region of the M bovis genome.1 That same year, an infant tuberculosis contact was given the first dose of this live attenuated vaccine, M bovis Bacille Calmette-Geurin (BCG). Now, with over 3 billion doses administered, BCG is the most widely used vaccine worldwide.

Since its first use 90 years ago, BCG has been recommended as a vaccine because of its partial protective effect against active tuberculosis and death, albeit with greater efficacy against disseminated and meningeal disease in children than pulmonary disease in adolescents and adults.2 3 This, taken together with autopsy studies suggesting BCG decreases the size of pulmonary tuberculous foci thereby limiting bacillary multiplication and spread4 and animal models where BCG vaccination reduces bacillary burden after M tuberculosis challenge but does not protect against infection, led to the longstanding dogma that BCG protects against dissemination and disease but not against infection. It was only 5 years ago that the first report5 of the ability of BCG to protect against the acquisition of infection changed …