BCG sub-strains induce variable protection against virulent pulmonary Mycobacterium tuberculosis infection, with the capacity to drive Th2 immunity

Abstract

The hallmark of a vaccine is to induce long-term protective immunity against the pathogen. The use of Mycobacterium bovis BCG as a vaccine against tuberculosis has been problematic in that immunity induced by BCG wanes over time and it may be less effective against more virulent strains of Mycobacterium tuberculosis. Thus it is important to determine what factors might be associated with waning or inefficient immunity. One such factor has been associated with the difference in many types of BCG that are used around the world, or more specifically due to the loss of genomic material in the various sub-strains used in vaccination programs. To address this issue we investigated the long-term immune response generated by 3 sub-strains BCG in the C57BL/6 mouse model of experimental tuberculosis. Mice vaccinated with these diverse strains of BCG were assessed at 6 and 12 months post-vaccination. All BCG sub-strain induced elevated levels of IFN-γ-producing cells at each time point as determined by ELISpot assay. However, when mice were challenged at 6 and 12 months with either M. tuberculosis H37Rv or HN878 the ability of the BCG sub-strains to protect vaccinated mice varied, depending on the time of challenge and on the strain used to infect mice. BCG Pasteur was then used to vaccinate guinea pigs, which were subsequently infected with either H37Rv or HN878. Data showed that BCG Pasteur prolonged the survival of guinea pigs against infection with both strains. Taken together these data suggest that longevity of the immune response generated by BCG is not related to the loss of genetic material and that BCG can induce a protective immune response to infection with a clinical strain of M. tuberculosis.