Characterization of major factors in the protective efficacy of a live attenuated vaccine against Mycobacterium tuberculosis using the naturally attenuated Mycobacterium microti in the murine model

Tuberculosis remains a major global health problem and is a one of the leading causes of morbidity and mortality by an infectious agent, especially in developing countries. Multi-drug resistance, limited resources, treatment expense and failure, HIV/AIDS epidemic, are all factors that necessitate the need for a better vaccine. The current licensed vaccine BCG has proven ineffective in fighting against the epidemic. Mycobacterium microti, also known as the vole bacillus, is naturally attenuated and has documented evidence of safety and efficacy in human populations. M. microti is reintroduced as a possible alternative to BCG vaccination and a model for live-attenuated vaccination against tuberculosis. The following experiments in mice confirmed the natural attenuation and efficacy of M. microti and the effectiveness of the oral route of administration of live vaccines against tuberculosis. The protection afforded by oral vaccination may be a consequence of an earlier immune response characterized by memory T cells and IFN-gamma production. This thesis focuses on a few factors important in live vaccination with M. microti. We compared our findings to other published literature in the field using a meta-analysis of vaccine experiments in inbred mice. Overall, there was a high rate of variability and inconsistency among these studies. In order to evaluate adequately vaccines against tuberculosis in laboratory animals such as the mouse and to obtain the most relevant information, there needs to be standardization of research design in vaccination studies to introduce more efficiently and effectively high-quality candidates for human testing.