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Journal of Virology, September 2005, p. 11095-11104, Vol. 79, No. 17
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.17.11095-11104.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Monoclonal Antibody AP33 Defines a Broadly Neutralizing Epitope on the Hepatitis C Virus E2 Envelope Glycoprotein

Ania Owsianka,1,{dagger} Alexander W. Tarr,2,{dagger} Vicky S. Juttla,2 Dimitri Lavillette,3 Birke Bartosch,3 François-Loïc Cosset,3 Jonathan K. Ball,2* and Arvind H. Patel1*

MRC Virology Unit, Institute of Virology, University of Glasgow, Church Street, Glasgow G11 5JR, United Kingdom,1 Institute of Infection, Immunity and Inflammation and Division of Microbiology, University of Nottingham, Queen's Medical Centre, Nottingham NG7 2UH, United Kingdom,2 Laboratoire de Vectorologie Rétrovirale et Thérapie Génique, INSERM U412, IFR128 BioSciences Lyon-Gerland, Ecole Normale Supérieure de Lyon, 69364 Lyon Cedex 07, France3

Received 3 March 2005/ Accepted 1 June 2005

Hepatitis C virus (HCV) remains a significant threat to the general health of the world's population, and there is a pressing need for the development of new treatments and preventative vaccines. Here, we describe the generation of retrovirus-based pseudoparticles (HCVpp) incorporating a panel of full-length E1E2 clones representative of the major genotypes 1 through 6, and their application to assess the reactivity and neutralizing capability of antisera and monoclonal antibodies raised against portions of the HCV E2 envelope protein. Rabbit antisera raised against either the first hypervariable region or ectodomain of E2 showed limited and strain specific neutralization. By contrast, the monoclonal antibody (MAb) AP33 demonstrated potent neutralization of infectivity against HCVpp carrying E1E2 representative of all genotypes tested. The concentration of AP33 required to achieve 50% inhibition of infection by HCVpp of diverse genotypes ranged from 0.6 to 32 µg/ml. The epitope recognized by MAb AP33 is linear and highly conserved across different genotypes of HCV. Thus, identification of a broadly neutralizing antibody that recognizes a linear epitope is likely to be of significant benefit to future vaccine and therapeutic antibody development.

* Corresponding author. Mailing address for Arvind H. Patel: MRC Virology Unit, Church Street, Glasgow G11 5JR, United Kingdom. Phone: 44 (141) 330 4026. Fax: 44 (141) 337 2236. E-mail: a.patel{at}vir.gla.ac.uk. Mailing address for Jonathan K. Ball: Institute of Infection, Immunity and Inflammation and Division of Microbiology, University of Nottingham, Queen's Medical Centre, Nottingham NG7 2UH, United Kingdom. Phone: 44 115 970 9162. Fax: 44 115 970 9233. E-mail: Jonathan.Ball{at}nottingham.ac.uk.

{dagger} A.O. and A.W.T. contributed equally to this work.

Journal of Virology, September 2005, p. 11095-11104, Vol. 79, No. 17
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.17.11095-11104.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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