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Infect. Immun. doi:10.1128/IAI.00019-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

BCG Immunization Induces Protective Immunity in Mice Against Nine Different Mycobacterium tuberculosis Strains

Laboratory of Mycobacterial Diseases and Cellular Immunology, Center for Biologics Evaluation and Research, United States Food and Drug Administration, Bethesda, MD; Public Health Research Institute, Tuberculosis Center, International Center for Public Health, Newark, NJ

^* To whom correspondence should be addressed. Email: sheldon.morris{at}fda.hhs.gov.

	Abstract

Recent pre-clinical and epidemiologic studies have suggested that certain M. tuberculosis genotypes (in particular, Beijing lineage strains) may be resistant to M. bovis BCG vaccine-induced anti-tuberculosis 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 two 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 post-challenge 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 6 of 9 challenge strains. Although lung CFU values were lower in vaccinated mice for only 3 of 9 groups at 20 weeks post-challenge, significantly decreased lung inflammation was seen in all immunized animals relative to controls at 20 weeks post-challenge. Taken together, these data demonstrate that BCG vaccination protects against infection with diverse M. tuberculosis strains in the mouse model of pulmonary tuberculosis and suggests that strain specific resistance to BCG-induced protective immunity may be uncommon.