Grant: CIHR Fellowship

With 1.5 million deaths in 2020, tuberculosis (TB) is one of the most important global health priorities. Within Canada, TB has a disproportionate impact on Inuit communities, those with HIV and migrant populations. Global eradication goals are dependent on the development of a novel efficacious vaccine overcoming limitations of prior efforts. Previous vaccines focused on the adaptive, or learned aspect of the immune system, given its role in prevention of active disease. However, this aspect of the immune system does not appear to be critical in preventing initial infection. Instead we believe an early robust response in the lungs is needed for effective vaccination. MAIT (mucosal invariant T) cells are a potential bridge between the initial innate response and the later adaptive response. They play a role in early response to TB infection in the lungs, while also having properties suggesting memory, making them an intriguing target cell for an efficacious vaccine. My PhD will focus on understanding the role of MAIT cells in protective immunity in TB and leveraging these insights in vaccine development. To do this we will examine cryopreserved blood samples previously collected by collaborators in South Africa, from three cohorts of infants: 1) neonates 2) 9-week-olds who received BCG vaccine at birth 3) 9-week-olds who had delayed BCG vaccine. By comparing MAIT cells in these cohorts we will characterize the way in which these cells respond to TB exposure (through BCG vaccination). After this we will examine a cohort of adults with TB who underwent lung lavage and blood sampling at the time of diagnosis and following treatment. Comparisons will permit a detailed characterization of the role of these cells in the lungs during infection, and how they respond following removal of the stimuli, post treatment. Through this analysis we will be able to determine if these cells have memory, and thus how they can be utilized for future TB vaccine development.