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Journal of Virology, January 2008, p. 966-973, Vol. 82, No. 2
0022-538X/08/$08.00+0     doi:10.1128/JVI.01872-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Isolation and Characterization of Broadly Neutralizing Human Monoclonal Antibodies to the E1 Glycoprotein of Hepatitis C Virus{triangledown}

Jean-Christophe Meunier,1 Rodney S. Russell,1 Vera Goossens,2 Sofie Priem,2 Hugo Walter,2 Erik Depla,2 Ann Union,2 Kristina N. Faulk,1 Jens Bukh,1,3,4 Suzanne U. Emerson,1* and Robert H. Purcell1

Hepatitis Viruses and Molecular Hepatitis Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892,1 GENimmune, Ghent, Belgium,2 Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre,3 Department of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark4

Received 27 August 2007/ Accepted 19 October 2007

The relative importance of humoral and cellular immunity in the prevention or clearance of hepatitis C virus (HCV) infection is poorly understood. However, there is considerable evidence that neutralizing antibodies are involved in disease control. Here we describe the detailed analysis of human monoclonal antibodies (MAbs) directed against HCV glycoprotein E1, which may have the potential to control HCV infection. We have identified two MAbs that can strongly neutralize HCV-pseudotyped particles (HCVpp) bearing the envelope glycoproteins of genotypes 1a, 1b, 4a, 5a, and 6a and less strongly neutralize HCVpp bearing the envelope glycoproteins of genotype 2a. Genotype 3a was not neutralized. The epitopes for both MAbs were mapped to the region encompassing amino acids 313 to 327. In addition, robust neutralization was also observed against cell culture-adapted viruses of genotypes 1a and 2a. Results from this study suggest that these MAbs may have the potential to prevent HCV infection.

* Corresponding author. Mailing address: Molecular Hepatitis Section, LID, NIAID, NIH, Bldg. 50, Rm. 6537, 50 South Dr., MSC 8009, Bethesda, MD 20892-8009. Phone: (301) 496-2787. Fax: (301) 402-0524. E-mail: semerson{at}niaid.nih.gov

{triangledown} Published ahead of print on 31 October 2007.

Journal of Virology, January 2008, p. 966-973, Vol. 82, No. 2
0022-538X/08/$08.00+0     doi:10.1128/JVI.01872-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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