Non-Tuberculous Mycobacteria Interference with BCG-Current Controversies and Future Directions

The global tuberculosis (TB) epidemic caused by the bacterial pathogen Mycobacterium tuberculosis (M.tb) continues unabated. The Mycobacterium bovis bacillus Calmette–Guérin (BCG) vaccination is widely utilized worldwide to protect against infection with M.tb. BCG vaccine protection against TB has had widely varying results for reasons that are not well understood. BCG vaccine interference by non-tuberculosis (NTM) mycobacterial species has been implicated as the potential cause of reduced BCG vaccine efficacy against M.tb. Ongoing efforts to develop new vaccines for TB requires a thorough understanding of the effect of NTM exposure on BCG vaccine efficacy, which may ultimately be a critical determinant of success. We reviewed the conflicting reports on whether NTM interferes with the BCG vaccine, potential explanations to help resolve the controversy, and strategies for developing better animal models. Further studies are needed to longitudinally track the effects of NTM exposure on BCG vaccine-induced host-protective anti-TB immunity.