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

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, generat...

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Main Authors: Mesalam, Ahmed Atef, Desombere, Isabelle, Farhoudi, Ali, Van Houtte, Freya, Verhoye, Lieven, Ball, Jonathan, Dubuisson, Jean, Foung, Steven K.H., Patel, Arvind H., Persson, Mats A.A., Leroux-Roels, Geert, Meuleman, Philip
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Published: Elsevier 2018
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Online Access:https://eprints.nottingham.ac.uk/48359/
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author Mesalam, Ahmed Atef
Desombere, Isabelle
Farhoudi, Ali
Van Houtte, Freya
Verhoye, Lieven
Ball, Jonathan
Dubuisson, Jean
Foung, Steven K.H.
Patel, Arvind H.
Persson, Mats A.A.
Leroux-Roels, Geert
Meuleman, Philip
author_facet Mesalam, Ahmed Atef
Desombere, Isabelle
Farhoudi, Ali
Van Houtte, Freya
Verhoye, Lieven
Ball, Jonathan
Dubuisson, Jean
Foung, Steven K.H.
Patel, Arvind H.
Persson, Mats A.A.
Leroux-Roels, Geert
Meuleman, Philip
author_sort Mesalam, Ahmed Atef
building Nottingham Research Data Repository
collection Online Access
description 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.
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spelling nottingham-483592020-05-04T19:26:54Z https://eprints.nottingham.ac.uk/48359/ Development and characterization of a human monoclonal antibody targeting the N-terminal region of hepatitis C virus envelope glycoprotein E1 Mesalam, Ahmed Atef Desombere, Isabelle Farhoudi, Ali Van Houtte, Freya Verhoye, Lieven Ball, Jonathan Dubuisson, Jean Foung, Steven K.H. Patel, Arvind H. Persson, Mats A.A. Leroux-Roels, Geert Meuleman, Philip 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. Elsevier 2018-01-15 Article PeerReviewed Mesalam, Ahmed Atef, Desombere, Isabelle, Farhoudi, Ali, Van Houtte, Freya, Verhoye, Lieven, Ball, Jonathan, Dubuisson, Jean, Foung, Steven K.H., Patel, Arvind H., Persson, Mats A.A., 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 Hepatitis C virus; Envelope protein; Antibody; Entry; Vaccine http://www.sciencedirect.com/science/article/pii/S0042682217303690?via%3Dihub doi:10.1016/j.virol.2017.10.019 doi:10.1016/j.virol.2017.10.019
spellingShingle Hepatitis C virus; Envelope protein; Antibody; Entry; Vaccine
Mesalam, Ahmed Atef
Desombere, Isabelle
Farhoudi, Ali
Van Houtte, Freya
Verhoye, Lieven
Ball, Jonathan
Dubuisson, Jean
Foung, Steven K.H.
Patel, Arvind H.
Persson, Mats A.A.
Leroux-Roels, Geert
Meuleman, Philip
Development and characterization of a human monoclonal antibody targeting the N-terminal region of hepatitis C virus envelope glycoprotein E1
title Development and characterization of a human monoclonal antibody targeting the N-terminal region of hepatitis C virus envelope glycoprotein E1
title_full Development and characterization of a human monoclonal antibody targeting the N-terminal region of hepatitis C virus envelope glycoprotein E1
title_fullStr Development and characterization of a human monoclonal antibody targeting the N-terminal region of hepatitis C virus envelope glycoprotein E1
title_full_unstemmed Development and characterization of a human monoclonal antibody targeting the N-terminal region of hepatitis C virus envelope glycoprotein E1
title_short Development and characterization of a human monoclonal antibody targeting the N-terminal region of hepatitis C virus envelope glycoprotein E1
title_sort development and characterization of a human monoclonal antibody targeting the n-terminal region of hepatitis c virus envelope glycoprotein e1
topic Hepatitis C virus; Envelope protein; Antibody; Entry; Vaccine
url https://eprints.nottingham.ac.uk/48359/
https://eprints.nottingham.ac.uk/48359/
https://eprints.nottingham.ac.uk/48359/