BCG vaccine

Immune system

Engineering

Tuberculosis vaccines

Immunization

Infectious disease (medical specialty)

Disease

Tuberculosis

Vaccination

Immunity

Electrical engineering

Pathology

Mycobacterium tuberculosis

Transmission (telecommunications)

Immunology

Medicine

Nature Medicine

Tuberculosis (TB) remains the deadliest infectious disease1, and the widely used Bacillus Calmette–Guérin (BCG) vaccine fails to curb the epidemic. An improved vaccination strategy could provide a cost-effective intervention to break the transmission cycle and prevent antimicrobial resistance2,3. Limited knowledge of the host responses critically involved in protective immunity hampers the development of improved TB vaccination regimens. Therefore, assessment of new strategies in preclinical models to select the best candidate vaccines before clinical vaccine testing remains indispensable. We have previously established in rhesus macaques (Macaca mulatta) that pulmonary mucosal BCG delivery reduces TB disease where standard intradermal injection fails4,5. Here, we show that pulmonary BCG prevents infection by using a repeated limiting-dose Mycobacterium tuberculosis challenge model and identify polyfunctional T-helper type 17 (TH17) cells, interleukin-10 and immunoglobulin A as correlates of local protective immunity. These findings warrant further research into mucosal immunization strategies and their translation to clinical application to more effectively prevent the spread of TB. Delivery of the Bacillus Calmette–Guérin vaccine into the lungs but not the skin of rhesus macaques protects animals from infection with Mycobacterium tuberculosis, suggesting that immune responses elicited locally may be required for vaccine efficacy.

Prevention of tuberculosis infection and disease by local BCG in repeatedly exposed rhesus macaques