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Journal of Virology, June 2008, p. 6061-6066, Vol. 82, No. 12
0022-538X/08/$08.00+0     doi:10.1128/JVI.02475-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Definition of a Conserved Immunodominant Domain on Hepatitis C Virus E2 Glycoprotein by Neutralizing Human Monoclonal Antibodies{triangledown}

Zhen-Yong Keck,1 Ta-Kai Li,1 Jinming Xia,1 Meital Gal-Tanamy,2 Oakley Olson,1 Sophia H. Li,1 Arvind H. Patel,3 Jonathan K. Ball,4 Stanley M. Lemon,2 and Steven K. H. Foung1*

Department of Pathology, Stanford University School of Medicine, Stanford, California 94305,1 Center for Hepatitis Research, Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, Texas 77555-1073,2 MRC Virology Unit, Institute of Virology, University of Glasgow, Church Street, Glasgow G11 5JR, United Kingdom,3 Institute of Infection, Immunity and Inflammation, School of Molecular Medical Sciences, the University of Nottingham, Queen's Medical Centre, Nottingham NG7 2UH, United Kingdom4

Received 16 November 2007/ Accepted 2 April 2008

Development of a successful hepatitis C virus (HCV) vaccine requires the definition of neutralization epitopes that are conserved among different HCV genotypes. Five human monoclonal antibodies (HMAbs) are described that cross-compete with other antibodies to a cluster of overlapping epitopes, previously designated domain B. Each HMAb broadly neutralizes retroviral pseudotype particles expressing HCV E1 and E2 glycoproteins, as well as the infectious chimeric genotype 1a and genotype 2a viruses. Alanine substitutions of residues within a region of E2 involved in binding to CD81 showed that critical E2 contact residues involved in the binding of representative antibodies are identical to those involved in the binding of E2 to CD81.

* Corresponding author. Mailing address: Stanford Medical School Blood Center, 3373 Hillview Avenue, Palo Alto, CA 94304. Phone: (650) 723-6481. Fax: (650) 725-6610. E-mail: sfoung{at}stanford.edu

{triangledown} Published ahead of print on 9 April 2008.

Journal of Virology, June 2008, p. 6061-6066, Vol. 82, No. 12
0022-538X/08/$08.00+0     doi:10.1128/JVI.02475-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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