Grant: Doctoral: Vanier Canada Graduate Scholarships

Background: Human immunodeficiency virus (HIV) is a global health issue, with 36.9 million HIV-infected people in 2018. HIV exhausts the infected person's immune system to the point where it cannot properly fight infections. Despite treatment with anti-HIV drugs to stop virus replication, immune system exhaustion still occurs. Understanding how to reverse this exhaustion is critical in enhancing long-term well-being of HIV-infected people. We have shown that a protein, lymphocyte-activation gene 3 (LAG-3), inhibits immune cells from functioning in HIV infection. LAG-3 is like the handbrake of a car. If you leave the handbrake on while driving, the car will never reach its full-speed. So, with LAG-3 present, the immune system cannot reach its full potential and fight infections. Our lab has shown there is more LAG-3 on immune cells called invariant Natural Killer T (iNKT) cells of HIV-infected people. iNKT cells are essential to a strong immune response; if iNKT cells do not function properly due to LAG-3, the immune system cannot work optimally to protect individuals. Hypothesis: I will determine if by blocking LAG-3, we will remove its handbrake-effect, allowing iNKT cells to work properly, helping to restore the immune system in HIV-infected people. Approach & Importance: In the lab, immune cells from HIV-infected participants will be exposed to a protein, called an antibody, which binds LAG-3 and prevents its handbrake activity. Once LAG-3 is blocked, we determine if iNKT cell activity returns back to normal by measuring how well the iNKT cell now functions. LAG-3 blockades are already in clinical trials to reverse cancer-related immune exhaustion, but LAG-3 research in the HIV field is limited. My project is highly feasible and future applications are very relevant, as the goal is to provide data to ultimately move the LAG-3 exhaustion marker blockade into HIV treatment clinical trials. If successful, this opens doors to transformative approaches in HIV therapy.