Scientific Core (Core B) Project Summary The Scientific Core is designed to successfully recruit and monitor HCV-antibody-negative people who inject drugs (PWID) for HCV infection and to identify and characterize acute infections and reinfections by testing sera for HCV RNA and seroconversion with serial ALT and HCV RNA testing. The infrastructure of Core B was necessary for completion of the first trial of an HCV vaccine in people at risk of HCV infection and will be useful in potential future trials of HCV vaccines. Plasma, serum, and peripheral blood mononuclear cells will be collected from prior to infection, during infection, and through the time when infection outcome (clearance or persistence of virus as well as during reinfection. Samples are stored in the repository for use in Projects 1-4, as well as for other HCV investigators. Core B will also provide standardized serological testing to quantitate HCV envelope-specific antibodies in plasma or serum of humans or vaccinated animals. Quantitative analyses of vaccine-induced plasma or serum antibody responses are essential to identify the most promising vaccine candidates. By applying a standardized set of assays to samples post-vaccination and from humans who successfully cleared multiple HCV infections, we will be able to make quantitative and qualitative comparisons between vaccine-induced antibody responses in mice or nonhuman primates (Projects 3 and 5) and human responses that are protective against HCV in vivo (Project 2). This will facilitate identification the vaccines most likely to be protective when advanced to human trials.