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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

Authors

Ahmed Atef Mesalam

Isabelle Desombere

Ali Farhoudi

Freya Van Houtte

Lieven Verhoye

JONATHAN BALL jonathan.ball@nottingham.ac.uk
Professor of Molecular Virology

Jean Dubuisson

Steven K.H. Foung

Arvind H. Patel

Mats A.A. Persson

Geert Leroux-Roels

Philip Meuleman



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.

Journal Article Type Article
Publication Date Jan 15, 2018
Journal Virology
Print ISSN 0042-6822
Electronic ISSN 0042-6822
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 514
APA6 Citation Mesalam, A. A., Desombere, I., Farhoudi, A., Van Houtte, F., Verhoye, L., Ball, J., …Meuleman, P. (2018). Development and characterization of a human monoclonal antibody targeting the N-terminal region of hepatitis C virus envelope glycoprotein E1. Virology, 514, https://doi.org/10.1016/j.virol.2017.10.019
DOI https://doi.org/10.1016/j.virol.2017.10.019
Keywords Hepatitis C virus; Envelope protein; Antibody; Entry;
Vaccine
Publisher URL http://www.sciencedirect.com/science/article/pii/S0042682217303690?via%3Dihub
Copyright Statement Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by-nc-nd/4.0

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Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by-nc-nd/4.0





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