SPHINX

"Spontaneous clearance in Patients acutely infected with HCV - Immune profiling, Novel biomarkers and X-omics approaches"

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 Obiettivo del progetto (Objective)

'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.'

Introduzione (Teaser)

Obtaining a greater understanding of how the immune system can clear hepatitis C virus (HCV) infection is the subject of the Sphinx project. This EU-Egypt alliance is expected to identify novel disease biomarkers and develop the necessary technological advances for early HCV diagnosis.

Descrizione progetto (Article)

Hepatitis C is a major public health problem with high incidence in regions such as Egypt and other Mediterranean countries. Chronically infected individuals are at risk of developing cirrhosis, hepatocellular carcinoma (HCC) and non-Hodgkin's lymphoma.

Unlike other chronic infections such as HIV, clearance of HCV is possible. Such clearance may occur spontaneously during the acute phase of infection or in response to therapeutic administration of type I interferon (IFN). A greater understanding of this phenomenon could help design prophylactic HCV vaccines to boost immune activity.

The EU-funded Sphinx initiative wishes to identify novel biomarkers, and provide new insight into the mechanisms of spontaneous clearance of HCV during acute infection. Project partners plan to use omics technologies to characterise the HCV-specific cellular immune response during the clearance phase, and assess any genetic and epigenetic variations that could potentially predict viral clearance.

A prime objective of the Sphinx initiative is the recruitment of a HCV patient cohort and the establishment of a central database with clinical, epidemiological and biological data for all patients. Protein signatures have been obtained for patients with hepatitis A, B or C infection and are currently being validated as disease biomarkers.

In order to analyse the immune cell activation during spontaneous clearance of HCV, scientists are performing database and in silico search. This has led to the identification of T cell epitopes specific for HCV genotype 4, as well as epitopes shared among different virus genotypes.

Additionally, the consortium is interested in performing a genetic analysis of polymorphisms in various genes in order to identify potential correlations with spontaneous resolution of HCV. A total of 43 genes have been selected with particular emphasis on the IL28B gene.

The support of scientific exchanges between partners has provided training opportunities in clinical epidemiology and biomarker discovery. Coupled with the developed assays, Sphinx project outcomes have the potential to improve and speed up identification of patients presenting with acute HCV.

Furthermore, new knowledge about acute HCV disease pathogenesis will lead to better disease management and prompt therapeutic intervention for those who require it.