This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Demangel, C. Articles by Cole, S. T. Search for Related Content PubMed PubMed Citation Articles by Demangel, C. Articles by Cole, S. T.

 Previous Article  |  Next Article 

Infection and Immunity, April 2005, p. 2190-2196, Vol. 73, No. 4
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.4.2190-2196.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Differential Effects of Prior Exposure to Environmental Mycobacteria on Vaccination with Mycobacterium bovis BCG or a Recombinant BCG Strain Expressing RD1 Antigens

Unité de Génétique Moléculaire Bactérienne, Institut Pasteur, Paris, France,¹ Department of Infectious Disease Immunology, Statens Serum Institut, Copenhagen, Denmark²

Received 19 October 2004/ Returned for modification 23 November 2004/ Accepted 15 December 2004

In silico analysis reveals that most protective antigens expressed by the antituberculous vaccine Mycobacterium bovis BCG (BCG) are conserved in M. avium, supporting the hypothesis that exposure to environmental mycobacteria generates cross-reactive immune responses blocking BCG activity. We investigated the impact of sensitization with M. avium, M. scrofulaceum, or M. vaccae on the protective efficacy of a recombinant BCG strain expressing RD1 antigens (BCG::RD1), using a mouse model of experimental tuberculosis (TB). No evidence that the RD1-encoded antigens ESAT-6, CFP-10, and PPE68 were expressed by these environmental strains could be demonstrated by Western blot analysis. Mice sensitized with each of these strains did not prime cellular immune responses cross-reacting with the immunodominant ESAT-6. Importantly, clearance of BCG::RD1 from the lungs and spleens of mice exposed to each of the environmental strains before vaccination was minimal compared to that of BCG. In mice sensitized with M. avium, increased persistence of BCG::RD1 correlated with stronger antimycobacterial gamma interferon responses and enhanced protection against aerosol infection with M. tuberculosis, compared to BCG. In contrast, animals exposed to M. scrofulaceum or M. vaccae prior to vaccination with BCG or BCG::RD1 were better protected against TB than were the unsensitized controls. Our results suggest that the inhibitory effect of environmental mycobacteria on the protective efficacy of BCG depends critically on the extent of cross-recognition of antigens shared with the vaccine. In hosts sensitized with M. avium, potent immunogenicity of ESAT-6 and increased persistence of BCG::RD1 may allow this recombinant vaccine to overcome preexisting antimycobacterial responses.

Editor: J. L. Flynn

This article has been cited by other articles:

• Wu, B., Huang, C., Garcia, L., de Leon, A. P., Osornio, J. S., Bobadilla-del-Valle, M., Ferreira, L., Canizales, S., Small, P., Kato-Maeda, M., Krensky, A. M., Clayberger, C. (2007). Unique Gene Expression Profiles in Infants Vaccinated with Different Strains of Mycobacterium bovis Bacille Calmette-Guerin. Infect. Immun. 75: 3658-3664 [Abstract] [Full Text]  
• Young, S. L., Slobbe, L., Wilson, R., Buddle, B. M., de Lisle, G. W., Buchan, G. S. (2007). Environmental Strains of Mycobacterium avium Interfere with Immune Responses Associated with Mycobacterium bovis BCG Vaccination. Infect. Immun. 75: 2833-2840 [Abstract] [Full Text]  
• Brosch, R., Gordon, S. V., Garnier, T., Eiglmeier, K., Frigui, W., Valenti, P., Dos Santos, S., Duthoy, S., Lacroix, C., Garcia-Pelayo, C., Inwald, J. K., Golby, P., Garcia, J. N., Hewinson, R. G., Behr, M. A., Quail, M. A., Churcher, C., Barrell, B. G., Parkhill, J., Cole, S. T. (2007). Genome plasticity of BCG and impact on vaccine efficacy. Proc. Natl. Acad. Sci. USA 104: 5596-5601 [Abstract] [Full Text]  
• Flaherty, D. K., Vesosky, B., Beamer, G. L., Stromberg, P., Turner, J. (2006). Exposure to Mycobacterium avium can modulate established immunity against Mycobacterium tuberculosis infection generated by Mycobacterium bovis BCG vaccination. J. Leukoc. Biol. 80: 1262-1271 [Abstract] [Full Text]  
• Castillo-Rodal, A. I., Castanon-Arreola, M., Hernandez-Pando, R., Calva, J. J., Sada-Diaz, E., Lopez-Vidal, Y. (2006). Mycobacterium bovis BCG Substrains Confer Different Levels of Protection against Mycobacterium tuberculosis Infection in a BALB/c Model of Progressive Pulmonary Tuberculosis. Infect. Immun. 74: 1718-1724 [Abstract] [Full Text]