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Clinical and Vaccine Immunology, May 2008, p. 750-756, Vol. 15, No. 5
1071-412X/08/$08.00+0     doi:10.1128/CVI.00018-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Immune Response Induced by Three Mycobacterium bovis BCG Substrains with Diverse Regions of Deletion in a C57BL/6 Mouse Model{triangledown}

S. M. Irwin,1 A. Goodyear,1 A. Keyser,1 R. Christensen,1 J. M. Troudt,1 J. L. Taylor,1 A. Bohsali,2 V. Briken,2 and A. A. Izzo1*

Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado 80524,1 Cell Biology and Molecular Genetics, University of Maryland, College Park, Maryland 207422

Received 15 January 2008/ Returned for modification 13 February 2008/ Accepted 7 March 2008

This study was performed to examine the adaptive immune response generated by three Mycobacterium bovis bacillus Calmette-Guérin (BCG) substrains to determine if the number of genomic regions of deletion played a significant role in determining the magnitude of the immune response or affected their ability to reduce the bacterial burden following low-dose aerosol challenge with a virulent M. tuberculosis strain. BCG Connaught, Pasteur, and Sweden were chosen as representative substrains, as they possessed many, intermediate, and few regions of deletion, respectively, as a result of changes in the genome in various regions. Mice were vaccinated subcutaneously and were then examined at 14, 21, and 42 days postvaccination. BCG was observed in the spleen, lung, and lymph nodes. BCG Connaught induced a greater pulmonary T-cell response than the other two substrains at day 14 postvaccination, although by 42 days postvaccination activated T-cell levels dropped to the levels observed in control mice for all three substrains. Among the three substrains, BCG Connaught induced significantly greater levels of interleukin-12 in bone marrow-derived macrophage cultures. Mice challenged at days 14, 21, and 42 postvaccination displayed an equal capacity to reduce the bacterial burden in the lungs and spleen. The data provide evidence that although the BCG substrains generated qualitatively and quantitatively different immune responses, they induced similar reductions in the bacterial burden against challenge with a virulent M. tuberculosis strain in the mouse model of tuberculosis. The data raise questions about the assessment of vaccine immune responses and the relationship to a vaccine's ability to reduce the bacterial burden.

* Corresponding author. Mailing address: Colorado State University, Department of Microbiology, Immunology & Pathology, 1682 Campus Delivery, Fort Collins, CO 80523. Phone: (970) 491-4350. Fax: (970) 491-1815. E-mail: Angelo.Izzo{at}colostate.edu

{triangledown} Published ahead of print on 19 March 2008.

Clinical and Vaccine Immunology, May 2008, p. 750-756, Vol. 15, No. 5
1071-412X/08/$08.00+0     doi:10.1128/CVI.00018-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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