Core B: Clinical Core Abstract Hepatitis C virus (HCV) is a virus that infects the liver and is transmitted through contaminated blood. HCV infection is still a public health priority and a major cause of liver disease worldwide, especially in developing countries like Egypt. New HCV infections are also on the rise in North America in association with the opioid epidemic. While new antiviral drug can cure >95% of infected individuals, many do not know that they are infected and remain at risk of developing liver disease and an active source of new infections. Furthermore, successful treatment does not prevent reinfection if the individual is re-exposed to the virus. 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 people who inject drugs at risk of HCV infection. This means that we need to understand better the immune factors and cells that protect against HCV in cohorts of patients who are able to clear the virus spontaneously. The main goal of this proposal is to define these factors that are essential to achieve protective immunity. The aim of this clinical core is to oversee and manage two cohorts of subjects that are infected with HCV to define these protective immune factors. The first cohort is located in Montreal and is a cohort of people who inject drugs who were able to clear two subsequent infections with HCV, a response that we would like to simulate in a vaccine. This cohort is already established (15 years), will recruit new subjects throughout the project and already has banked samples from many reinfection cases to start the projects right away. It will also include a smaller subcohort of PWID, primarily infected with genotypes 1 and 3, undergoing antiviral treatment. The second is a large cohort of individuals undergoing antiviral therapy for HCV from Egypt, the country with the highest number of HCV infections in the world. This second cohort is primarily infected with genotype 4 and will allow us to understand whether curing HCV infection using antiviral treatments will enhance these protective immune factors and cells. By collecting well defined blood samples and clinical data about disease progression and virus from these precious cohorts, we will be able to study the HCV-specific immune response and identify the immune factors that should be targeted in novel vaccines.