Failure of the Mycobacterium bovis BCG vaccine: some species of environmental mycobacteria block multiplication of BCG and induction of protective immunity to tuberculosis

Infect Immun. 2002 Feb;70(2):672-8. doi: 10.1128/IAI.70.2.672-678.2002.


The efficacy of Mycobacterium bovis bacillus Calmette-Guérin (BCG) vaccine against pulmonary tuberculosis (TB) varies enormously in different populations. The prevailing hypothesis attributes this variation to interactions between the vaccine and mycobacteria common in the environment, but the precise mechanism has so far not been clarified. Our study demonstrates that prior exposure to live environmental mycobacteria can result in a broad immune response that is recalled rapidly after BCG vaccination and controls the multiplication of the vaccine. In these sensitized mice, BCG elicits only a transient immune response with a low frequency of mycobacterium-specific cells and no protective immunity against TB. In contrast, the efficacy of TB subunit vaccines was unaffected by prior exposure to environmental mycobacteria. Six different isolates from soil and sputum samples from Karonga district in Northern Malawi (a region in which BCG vaccination has no effect against pulmonary TB) were investigated in the mouse model, and two strains of the Mycobacterium avium complex were found to block BCG activity completely.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyltransferases*
  • Animals
  • Antigens, Bacterial / immunology
  • BCG Vaccine / immunology*
  • BCG Vaccine / therapeutic use
  • Bacterial Proteins / immunology
  • Cells, Cultured
  • Female
  • Lymphocytes / cytology
  • Malawi
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred CBA
  • Mycobacterium Infections, Nontuberculous / immunology
  • Mycobacterium Infections, Nontuberculous / prevention & control*
  • Mycobacterium avium Complex / immunology*
  • Mycobacterium bovis / growth & development
  • Mycobacterium bovis / immunology
  • Mycobacterium chelonae / immunology*
  • Mycobacterium fortuitum / immunology*
  • Mycobacterium scrofulaceum / immunology*
  • Spleen / cytology
  • Tuberculosis, Pulmonary / immunology
  • Tuberculosis, Pulmonary / prevention & control


  • Antigens, Bacterial
  • BCG Vaccine
  • Bacterial Proteins
  • ESAT-6 protein, Mycobacterium tuberculosis
  • Acyltransferases
  • antigen 85B, Mycobacterium tuberculosis