SPHINX 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).
This project 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.
Specifically, we aim to use “-omics” or hypothesis-generating approaches to perform :
- multi-analyte profiling of plasma analytes;
- characterization of HCV-specific cellular immune responses during the clearance phase; and
- 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 (the Science and Technology Development Fund) will further enhance the impact of the proposed work.
Our Consortium is in an unparalleled position to study the pathogenesis of acute HCV infection in regions where disease incidence is high and the recruitment of acute symptomatic HCV individuals permits the establishment of relevant patient cohorts. We will exploit this unique position by assessing which host factors are critical for spontaneous clearance, by preventing HCV entry into uninfected cells or allowing for rapid targeting of HCV infected hepatocytes. Relevant host factors that will be analyzed by the Consortium include metabolic analytes, innate immune molecules and components of the cellular and humoral immune system. Determinants of the host response include the expression of regulatory micro-RNAs (miRNAs) and genetic polymorphisms, both of which may serve as potential biomarkers, but also provide a mechanistic understanding of how a minority of infected individuals clear the virus without therapeutic intervention.
Results obtained from this project will impact the management of acute hepatitis C in Egypt; provide critical tools for studying the host response to HCVg4; and though the delivery of greater insight into the mechanisms of spontaneous clearance, we will identify potential correlates of vaccine protection.