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Clin. Vaccine Immunol. doi:10.1128/CVI.00018-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Analysis of the immune response in the C57BL/6 mouse model induced by three Mycobacterium bovis BCG sub-strains with diverse regions of deletion

Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO 80524, and Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742

^* To whom correspondence should be addressed. Email: Angelo.Izzo{at}colostate.edu.

	Abstract

This study was performed to examine the adaptive immune response generated by three Mycobacterium bovis, BCG sub-strains 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 virulent M. tuberculosis. BCG Connaught, Pasteur and Sweden were chosen as representative sub-strains as they possessed many, intermediate and few regions of deletion respectively, when compared to changes in the genome in various regions. Mice were vaccinated subcutaneously and then examined at 14, 21 and 42 days post-vaccination. BCG was observed in the spleen, lung and lymph nodes. BCG Connaught induced a greater pulmonary T cell response than the other two sub-strains at day 14 post-vaccination, although by 42 days post-vaccination activated T cell levels dropped to levels observed in control mice for all three sub-strains. Amongst the three sub-strains, BCG Connaught induced significantly greater levels of IL-12 in bone marrow derived macrophage cultures. Mice challenged at days 14, 21 and 42 post-vaccination displayed an equal capacity to reduce the bacterial burden in the lungs and spleen. The data provide evidence that although BCG sub-strains generate qualitatively and quantitatively different immune responses, they induce a similar reduction in bacterial burden against challenge with virulent M. tuberculosis in the mouse model of tuberculosis. The data raise questions about assessing vaccine immune responses and the relationship to a vaccines ability to reduce the bacterial burden.