The bacille Calmette–Guérin vaccine can protect children from tuberculosis (TB), but is not effective in adults, probably owing to Mycobacterium tuberculosis (Mtb) manipulating human innate immune responses to enable persistent infection. A recent study reports a promising alternative vaccine approach — the use of cytomegalovirus vectors encoding Mtb antigen inserts. “Our approach works in a highly Mtb-susceptible species — rhesus monkeys — challenged with a highly pathogenic Mtb strain. For the first time, we saw a vaccine completely control Mtb challenge in a substantial proportion of vaccinated animals, such that the innate immune response to challenge was largely abrogated, and no granulomatous disease developed,” notes Louis Picker, lead author of the study. The authors plan to refine the vaccine and further understand the mechanisms mediating protection.