This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental material
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Jeon, B. Y.
Right arrow Articles by Morris, S. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Jeon, B. Y.
Right arrow Articles by Morris, S. L.

 Previous Article  |  Next Article 

Infection and Immunity, November 2008, p. 5173-5180, Vol. 76, No. 11
0019-9567/08/$08.00+0     doi:10.1128/IAI.00019-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Mycobacterium bovis BCG Immunization Induces Protective Immunity against Nine Different Mycobacterium tuberculosis Strains in Mice{triangledown} ,{dagger}

Bo Young Jeon,1,{ddagger} Steven C. Derrick,1 JaeHyun Lim,1 Kristopher Kolibab,1 Veerabadran Dheenadhayalan,1,§ Amy Li Yang,1 Barry Kreiswirth,2 and Sheldon L. Morris1*

Laboratory of Mycobacterial Diseases and Cellular Immunology, Center for Biologics Evaluation and Research, United States Food and Drug Administration, Bethesda, Maryland,1 Public Health Research Institute, Tuberculosis Center, International Center for Public Health, Newark, New Jersey2

Received 7 January 2008/ Returned for modification 2 March 2008/ Accepted 13 August 2008

Recent preclinical and epidemiologic studies have suggested that certain Mycobacterium tuberculosis genotypes (in particular, Beijing lineage strains) may be resistant to Mycobacterium bovis BCG vaccine-induced antituberculosis protective immunity. To investigate the strain specificity of BCG-induced protective responses in a murine model of pulmonary tuberculosis, C57BL/6 mice were vaccinated with BCG vaccine and then challenged 2 months later with one of nine M. tuberculosis isolates. Four of these strains were from the W-Beijing lineage (HN878, N4, NHN5, and ChS) while four were non-Beijing-type isolates (C913, CDC1551, NY669, and NY920). As a control, the WHO standard M. tuberculosis Erdman strain was evaluated in these vaccination/challenge experiments. To assess the protective responses evoked by BCG immunization, organ bacterial burdens and lung pathology were assessed in vaccinated and naïve mice at 4, 12, and 20 weeks postchallenge as well as during the day of infection. At 4 weeks after the aerosol challenge with each of these strains, significantly reduced bacterial growth in the lungs and spleens and significantly improved lung pathology were seen in all vaccinated animals compared to naïve controls. After 12 weeks, reduced organ bacterial burdens were detected in vaccinated animals infected with six of nine challenge strains. Although lung CFU values were lower in vaccinated mice for only three of nine groups at 20 weeks postchallenge, significantly decreased lung inflammation was seen in all immunized animals relative to controls at 20 weeks postchallenge. Taken together, these data demonstrate that BCG vaccination protects against infection with diverse M. tuberculosis strains in the mouse model of pulmonary tuberculosis and suggest that strain-specific resistance to BCG-induced protective immunity may be uncommon.

* Corresponding author. Mailing address: FDA/CBER, Building 29, Room 502, 29 Lincoln Drive, Bethesda, MD 20892. Phone: (301) 496-5978. Fax: (301) 435-5675. E-mail: sheldon.morris{at}fda.hhs.gov

{triangledown} Published ahead of print on 18 August 2008.

{dagger} Supplemental material for this article may be found at http://iai.asm.org/.

Editor: J. L. Flynn

{ddagger} Present address: Department of Microbiology, Yonsei University College of Medicine, Seoul, South Korea.

§ Present address: Aeras Global TB Vaccine Foundation, Rockville, MD.

Infection and Immunity, November 2008, p. 5173-5180, Vol. 76, No. 11
0019-9567/08/$08.00+0     doi:10.1128/IAI.00019-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Einarsdottir, T., Lockhart, E., Flynn, J. L. (2009). Cytotoxicity and Secretion of Gamma Interferon Are Carried Out by Distinct CD8 T Cells during Mycobacterium tuberculosis Infection. Infect. Immun. 77: 4621-4630 [Abstract] [Full Text]  
  • Marais, B. J., Hesseling, A. C., Schaaf, H. S., Gie, R. P., van Helden, P. D., Warren, R. M. (2009). Mycobacterium tuberculosis Transmission Is Not Related to Household Genotype in a Setting of High Endemicity. J. Clin. Microbiol. 47: 1338-1343 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»