Grant: Project Grant

Hepatitis C virus (HCV) infection is still a public health priority as many remain undiagnosed and increased infections in association with the opioid epidemic. Direct acting antivirals offer complete cure in >95% of infected individuals but do not prevent reinfection. Furthermore, HCV disproportionately affects some populations with limited access to health services and who remain at high risk of HCV infection and reinfection like Indigenous peoples, people who use drugs (PWUD), newcomers to Canada, men who have sex with men and others. Hence, there is an urgent need for vaccines that can protect against this virus. Unfortunately, despite our knowledge about the immune response against HCV, we still do not have an effective vaccine. Recent results from the only vaccine candidate that made it into a large scale (Phase 2) clinical trial did not show any protection in PWUD at risk of HCV infection. This means that we have to understand better the immune factors that protect against HCV. This project will examine what constitutes such a good immune response by studying immunity in a group of PWUD who are constantly being exposed to the virus where some are able to clear it several times and others cannot. We will identify the differences in those who clear the viruses and those who cannot. We will also compare the immune response in individuals who clear the virus spontaneously versus those who clear it post treatment to determine if they are less protected against HCV if they are re-exposed to it. We will use the latest 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 a protective immune response. We will attempt to use chemical compounds to correct the defects observed in those who are unable to clear the virus. Such compounds can be combined with different vaccine candidates to enhance their immunogenicity and protective capacity.