Abstract In this program, we propose to determine the correlates of protection in individuals that spontaneously clear multiple HCV infection episodes. This will give highly valuable information for the design of next generation of vaccines. Our goal to assess the role of antigen-specific T and B cell responses in infection outcome and to generate an efficacious immune response by vaccination strategies in non-human primates based on emulating successful resolution of natural re-exposure and re-infection in human patients. This U19 proposal consists of 3 Projects and two Cores consisting of an Administrative Core A and a Clinical Core B. The Administrative Core A will provide two functions: (i) provide overall administrative oversight and support for the Program and (ii) provide biostatistical analyses and data management support for the individual projects and Cores. This Administrative Core will be led by Dr. Grakoui at Emory University and will provide the coordination necessary to make effective and efficient use of resources and intermediate results from this collaborative effort. The primary function will be to facilitate scientific interactions between the Project leaders as well as Core leaders. The administrative component will provide the leadership to ensure milestones are met, assessment of the Core functions, modification of scientific goals, incorporation of any new collaborators, decisions of ongoing prioritization and reallocation of resources. Critical decisions will be made in consultation with the Project leaders and program official at NIH. The Administrative Core will file annual reports to the NIH. The Administrative Core will maintain budgets and oversee any re-budgeting that is needed to meet program goals. The biostatistics portion of the Administrative Core will provide data management and statistical support for the three projects. In addition, the Biostatics portion will establish and maintain appropriate database, management and analysis in response to investigators' requests. In order to provide services to meet the analytical challenges the Core will include facilitating methodologies necessary for addressing complex statistical issues encountered in various research projects. In addition, provide essential metrics between the clinicians, scientists and biostatisticians. Having resources dedicated to the biostatistics and data management needs for the research proposed here, will add enormous value to the quality and productivity of the research conducted by the Investigators and to disseminate this information correctly to the scientific community.