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Virology. 2018 Jan 15;514:30-41. doi: 10.1016/j.virol.2017.10.019. Epub 2017 Nov 10.

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

Author information

1
Department of Clinical Chemistry, Microbiology and Immunology, Ghent University, Ghent, Belgium; Therapeutic Chemistry Department, National Research Centre (NRC), Dokki, Cairo, Egypt. Electronic address: Ahmed.Mesalam@ugent.be.
2
Department of Clinical Chemistry, Microbiology and Immunology, Ghent University, Ghent, Belgium. Electronic address: Isabelle.Desombere@wiv-isp.be.
3
Department of Clinical Chemistry, Microbiology and Immunology, Ghent University, Ghent, Belgium. Electronic address: Ali.Farhoudi@ugent.be.
4
Department of Clinical Chemistry, Microbiology and Immunology, Ghent University, Ghent, Belgium. Electronic address: Freya.VanHoutte@ugent.be.
5
Department of Clinical Chemistry, Microbiology and Immunology, Ghent University, Ghent, Belgium. Electronic address: Lieven.Verhoye@ugent.be.
6
School of Life Sciences, The University of Nottingham, Nottingham NG7 2RD, UK; Nottingham Digestive Diseases Centre, National Institute for Health Research (NIHR) Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and The University of Nottingham, Nottingham NG7 2UH, UK. Electronic address: Jonathan.Ball@nottingham.ac.uk.
7
Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 8204 - CIIL - Center for Infection & Immunity of Lille, F-59000 Lille, France. Electronic address: Jean.Dubuisson@ibl.cnrs.fr.
8
Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA. Electronic address: sfoung@stanford.edu.
9
MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow, UK. Electronic address: Arvind.Patel@glasgow.ac.uk.
10
Karolinska Institutet, Department of Clinical Neurosciences, Center for Molecular Medicine, Karolinska University Hospital Solna, 171 76 Stockholm, Sweden. Electronic address: Mats.Persson@ki.se.
11
Department of Clinical Chemistry, Microbiology and Immunology, Ghent University, Ghent, Belgium. Electronic address: Geert.LerouxRoels@ugent.be.
12
Department of Clinical Chemistry, Microbiology and Immunology, Ghent University, Ghent, Belgium. Electronic address: Philip.Meuleman@ugent.be.

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.

KEYWORDS:

Antibody; Entry; Envelope protein; Hepatitis C virus; Vaccine

PMID:
29128754
PMCID:
PMC5784761
DOI:
10.1016/j.virol.2017.10.019
[Indexed for MEDLINE]
Free PMC Article

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