Grant: Operating Grant - PA: Bridge Funding -CHVI Vaccine Discovery and Social Research

Every year, millions of people die from Mycobacterium tuberculosis infection, the causative agent of Tuberculosis (TB), which is a treatable infectious disease. It is estimated that one-third of the worlds population is infected with TB, including one third of the 34 million people infected with HIV. The majority of individuals control TB infection in a hidden or latent state, however in 5-10% of people TB reactivates to cause disease. Co-infection with HIV drastically increases the chances of TB reactivation and has contributed greatly to the high number of deaths due to HIV both within Canada and worldwide. Progression of TB disease from latency to reactivation and clinical symptoms is a continuous process of bacterial replication and counterbalancing immune responses that are not well understood. We propose to study the immune responses to tuberculosis from latency, to TB reactivation, and following TB treatment in HIV/TB co-infected individuals in Nairobi, Kenya focusing on HIV high-risk female sex workers who are part of a well-established cohort supported by the University of Nairobi and the University of Manitoba. As TB is endemic in Kenya, this population is at very high risk of developing HIV/TB co-infection and this study represent an opportunity to better identify new diagnostics capable of identifying TB latency, TB activation, and TB cure in the context of HIV infection. We also propose to define immune responses specific to HIV over the spectrum of TB disease. This will provide important information on the effect that different stages of TB disease have on immune response to HIV and how this information may inform HIV and TB treatment options in populations where an HIV vaccine may eventually be used. Together, these studies will better inform our understanding of TB latency, reactivation, and disease as well as determine the effect of TB on HIV immunity and potential vaccine responses in the millions of HIV/TB co-infected people.