85 IL28B GENETIC STATUS IN ASSOCIATION WITH HCV SPECIFIC T-CELL IMMUNITY

Abstract

Introduction: Hepatitis E virus (HEV) infection usually results in an acute, self-limiting hepatitis in immunocompetent individuals while it may rarely progress to fulminant hepatic failure. Several cases of chronic evolution of HEV infections have been described recently in French, Dutch and German immunosuppressed patients. However immune correlates of clearance or persistence of HEV have not been described so far. Aims of this study were to i. investigate whether HEV persistence is associated with impaired immune responses and ii. identify potential epitopic regions in HEV genome that may elicit strong immune cellular responses to be considered for a potential vaccine. Methods: Immune responses against HEV were studied in a total of 29 subjects including 21 healthy immunocompetent individuals (anti-HEV-positive; n = 13 (“exposed”); anti-HEV-negative n =8 (“no exposure”)) and 8 anti-HEV-positive patients after organ transplantation. 4 transplanted patients evolved to chronic hepatitis while 4 subjects were followed and cleared HEV spontaneously. PBMCs were stimulated with HEV overlapping peptide pools (spanning ORF2 and ORF3) or individual peptides. T-cell proliferation was measured after 7 days by CFSE (5, 6-carboxyfluorescein diacetate succinimidyl ester) assay. Cytokine secretion was investigated by intra-cellular cytokine staining (IFN-gamma, MIP-1beta and TNF-alpha). Results: Multispecific (positive responses for more at least 2 peptide pools) and strong HEV-specific CD4/CD8 T-cell were detectable in 77%/62% of HEV-seropositive healthy subjects respectively. No HEV-specific responses were observed in any of the HEV-unexposed individuals. In transplant recipients, multispecific but moderate T-cell responses were detectable in resolved individuals while chronic patients did not show any specific T cell response. Using individual peptides, immune responses were narrowed-down to two epitopes that presented very strong CD8 responses. These results were further corroborated by cytokine production, where IFN-gamma and MIP-1beta secretion was observed only in seropositive healthy individuals. Conclusion: These results suggest that chronic HEV infection is associated with impaired HEV-specific adaptive immune responses. Identification of immunodominant epitopes may have implications for vaccine design. 85 IL28B GENETIC STATUS IN ASSOCIATION WITH HCV SPECIFIC T-CELL IMMUNITY C. Bucci, M. Rahman, I. Humphreys, A.C. Brown, M. Lucas, K. Pfafferott, J. Collier, D. O’Donnell, E. Stafford, P. Klenerman, S. Gaudieri, E. Barnes. Department of Hepatology, Nuffield Department of Medicine & Oxford NIHR BRC, Nuffield Department of Medicine, University of Oxford, Oxford, UK; Institute of Immunology and Infectious Diseases, Murdoch University, Perth, WA, Australia; Hepatology & Oxford NIHR BRC, University of Oxford, Oxford, UK; School of Anatomy and Human Biology and Centre for Forensic Science, University of Western Australia, Perth, WA, Australia E-mail: cristinabucci@hotmail.it