Development and characterization of a human monoclonal antibody targeting the N-terminal region of hepatitis C virus envelope glycoprotein E1

Mesalam, Ahmed Atef and Desombere, Isabelle and Farhoudi, Ali and Van Houtte, Freya and Verhoye, Lieven and Ball, Jonathan and Dubuisson, Jean and Foung, Steven K.H. and Patel, Arvind H. and Persson, Mats A.A. and Leroux-Roels, Geert and Meuleman, Philip (2018) Development and characterization of a human monoclonal antibody targeting the N-terminal region of hepatitis C virus envelope glycoprotein E1. Virology, 514 . pp. 30-41. ISSN 0042-6822

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Abstract

Monoclonal antibodies (mAbs) targeting the hepatitis C virus (HCV) envelope have been raised mainly against envelope protein 2 (E2), while the antigenic epitopes of envelope protein 1 (E1) are not fully identified. Here we describe the detailed characterization of a human mAb, designated A6, generated from an HCV genotype 1b infected patient. ELISA results showed reactivity of mAb A6 to full-length HCV E1E2 of genotypes 1a, 1b and 2a. Epitope mapping identified a region spanning amino acids 230-239 within the N-terminal region of E1 as critical for binding. Antibody binding to this epitope was not conformation dependent. Neutralization assays showed that mAb A6 lacks neutralizing capacity and does not interfere with the activity of known neutralizing antibodies. In summary, mAb A6 is an important tool to study the structure and function of E1 within the viral envelope, a crucial step in the development of an effective prophylactic HCV vaccine.

Item Type: Article
Keywords: Hepatitis C virus; Envelope protein; Antibody; Entry; Vaccine
Schools/Departments: University of Nottingham, UK > Faculty of Medicine and Health Sciences > School of Medicine > Nottingham Digestive Diseases Centre
University of Nottingham, UK > Faculty of Medicine and Health Sciences > School of Life Sciences
Identification Number: 10.1016/j.virol.2017.10.019
Depositing User: Eprints, Support
Date Deposited: 24 Nov 2017 09:43
Last Modified: 24 Nov 2017 09:53
URI: http://eprints.nottingham.ac.uk/id/eprint/48359

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