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Infection and Immunity, February 2002, p. 672-678, Vol. 70, No. 2
0019-9567/01/$04.00+0     DOI: 70.2.672-678.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Failure of the Mycobacterium bovis BCG Vaccine: Some Species of Environmental Mycobacteria Block Multiplication of BCG and Induction of Protective Immunity to Tuberculosis

Lise Brandt,1,{dagger} Joana Feino Cunha,2 Anja Weinreich Olsen,1 Ben Chilima,3,4 Penny Hirsch,4 Rui Appelberg,2 and Peter Andersen1*

Department of TB Immunology, Statens Serum Institut, Copenhagen, Denmark,1 Laboratory of MicrobiologyImmunology of Infection, Institute of Molecular and Cell Biology, University of Porto, Portugal,2 Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London,,3 Department of Soil Science, Institute of Arable Crops Research-Rothamsted, Hertfordshire, United Kingdom4

Received 15 August 2001/ Returned for modification 5 October 2001/ Accepted 7 November 2001

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.

* Corresponding author. Mailing address: Statens Serum Institut, Department of TB Immunology, Artillerivej 5, 2300 Copenhagen S, Denmark. Phone: 45 32683480. Fax: 45 32683035. E-mail: pa{at}0040ssi.dk.

Editor: S. H. E. Kaufmann

{dagger} Present address: Department of Microbiology, Colorado State University, Fort Collins, CO 80523.

Infection and Immunity, February 2002, p. 672-678, Vol. 70, No. 2
0019-9567/01/$04.00+0     DOI: 70.2.672-678.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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