"The proposed project aims to identify novel biomarkers and provide new insight into the mechanisms of spontaneous clearance of hepatitis C virus (HCV) during the early stages of acute infection. Indeed hepatitis C is a major public health problem with high incidence in regions such as Egypt and other Mediterranean Partner Countries (MPCs). Our current application follows from an FP5 project entitled “Promoting Healthy Societies: research in support of regional infectious disease surveillance,” which permitted development of a cohort of patients with acute symptomatic HCV. Herein, we propose to build on this program for biochemical, immunologic and gene polymorphism assessment of patients with an enriched Consortium of European, Egyptian and Tunisian academic institutions and one European SME. Our multi-national, inter-disciplinary Consortium is in a strong position to establish an in-depth understanding of spontaneous viral clearance and provide needed information that will impact patient management and the design of candidate vaccines for HCV genotype 4. Specifically, we aim to use “-omics” or hypothesis-generating approaches to perform: (i) multi-analyte profiling of plasma analytes; (ii) characterization of HCV-specific cellular immune responses during the clearance phase; and (iii) assessment of genetic and epigenetic variations that predict viral clearance. Together, this will provide a framework for understanding the host response to acute HCV. In addition, we aim to establish a cooperative training program under the umbrella of the EU/MPC Research Collaboration – Fighting Hepatitis in Egypt, which will enhance Clinical Epidemiology and Biomarker Discovery. Cross-Consortia collaborations with the EU funded HepaCute Project and Egyptian funded STDF will further enhance the impact of our proposed work."