Grant: CIHR Fellowship

Tuberculosis (TB) is a respiratory infection and the mostly deadly infectious disease known to man. Until date no effective vaccine is available to prevent disease in adults. Annually more than 1.5 million die of TB therefore an effective vaccine is a global health priority. A major stumbling block is that the immune parameters that define protection are unknown for TB. What complicates matters more is that unlike other infections, prior infection does not establish protective TB immunity. The main target of efforts to design an effective TB vaccine are conventional T cells. This immune cell population is critical to human immunity as they possess the capacity to establish a population of memory cells in response to infection. Despite being a necessary component of protective TB immunity, strategies that include targeting conventional T cells towards a TB vaccine have proven unsuccessful. Therefore it is necessary to explore alternative immune targets outside of the mainstream. Unconventional T cells are a subset of T cells that unfortunately have been understudied. This unique population is enriched in many organs, such as the skin, intestines and lungs. Several studies have shown that unconventional T cells are required for immune defense against infection. In addition, during the early stages of life unconventional T cells fulfill a critical role as other components of the immune system have yet to mature. This process of immune maturation is believed to be linked to the seeding of the gut microbiota. Therefore, we hypothesize that in early life the immune system receives important instructions that inform immune protection in later life. By intervening during the neonatal phase of life with a vaccine, such as the BCG vaccine, we aim to shape the immunity in such a manner to generate protection against TB throughout life. In particular we aim to study the role of unconventional T cells following neonatal vaccination and how this provides immune protection to TB.