Grant: Operating Grant

Development of vaccines against many viral infections is hindered by our limited understanding of what constitutes an efficient and protective immune response and what parameters can be used to evaluate the success of vaccine candidates. Hepatitis C virus (HCV) infection is transmitted through blood. The majority of individuals who become infected with this virus become persistently infected and develop chronic liver disease. However, a fraction of approximately 20% is able to eliminate the virus without therapeutic intervention. Given that most of these rare individuals are injection drug users (IDUs) who continue to be re-exposed to the virus, they represent a unique opportunity to study protection against a human viral infection in a real world setting. Such a natural experiment can only be examined in a handful of cohorts worldwide. We are the only Canadian group set to do this through our unique Montreal HCV cohort. We plan to study protective immunity by examining the different arms of the immune response in IDUs who have successfully cleared one or more HCV infection or have demonstrated long-term protection despite being repeatedly exposed to the virus. We will use the latest state-of-the-art technology to examine the immune response at the functional and genomic level and identify cellular pathways and key molecules that are implicated in the development and maintenance of immunological memory. The results obtained from such an analysis will be relevant to all human viral infections and will guide vaccine development against many pathogens.