Human monoclonal antibodies that react with the E2 glycoprotein of hepatitis C virus and possess neutralizing activity

Authors

  • Darren J. Schofield,

    1. Hepatitis Viruses, Laboratory of Infectious Diseases, NIAID, National Institutes of Health, Bethesda, MD
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  • Birke Bartosch,

    1. Laboratoire de Vectorologie Rétrovirale et Therapie Genique, Institut National de la Sante et de la Recherche Medicale 4412, IFR 128, Ecole Normale Supérieure de Lyon, Lyon, France
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  • Yohko K. Shimizu,

    1. Department of Respiratory Diseases, Research Institute, International Medical Center of Japan, Tokyo, Japan
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  • Tobias Allander,

    1. Hepatitis Viruses, Laboratory of Infectious Diseases, NIAID, National Institutes of Health, Bethesda, MD
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  • Harvey J. Alter,

    1. Department of Transfusion Medicine, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD
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  • Suzanne U. Emerson,

    1. Molecular Hepatitis Sections, Laboratory of Infectious Diseases, NIAID, National Institutes of Health, Bethesda, MD
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  • François-Loïc Cosset,

    1. Laboratoire de Vectorologie Rétrovirale et Therapie Genique, Institut National de la Sante et de la Recherche Medicale 4412, IFR 128, Ecole Normale Supérieure de Lyon, Lyon, France
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  • Robert H. Purcell

    Corresponding author
    1. Hepatitis Viruses, Laboratory of Infectious Diseases, NIAID, National Institutes of Health, Bethesda, MD
    • Hepatitis Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bldg. 50 Rm. 6523, 50 South Drive MSC-8009, Bethesda MD 20892-8009
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    • fax: 301-402-0524


  • Potential conflict of interest: Nothing to report.

Abstract

Active and/or passive immunoprophylaxis against hepatitis C virus (HCV) remain unachieved goals. Monoclonal antibodies might provide one approach to protection. We derived human monoclonal antibodies from the bone marrow of a patient with a well-controlled HCV infection of 22 years duration. Five distinct antibodies reactive with the E2 glycoprotein of the homologous 1a strain of HCV were recovered as antigen-binding fragments (FAbs). They demonstrated affinity constants as high as 2 nanomolar. “Neutralization of binding” titers paralleled the affinity constants. All five FAbs reacted with soluble E2 protein only in nonreducing gels, indicating that the relevant epitopes were conformational. The FAbs could be divided into two groups, based on competition analysis. Three of the FAbs neutralized the infectivity of pseudotyped virus particles (pp) bearing the envelope glycoproteins of the homologous HCV strain (genotype 1a). The three FAbs also neutralized genotype 1b pp and one also neutralized genotype 2a pp. In conclusion, one or more of these monoclonal antibodies may be useful in preventing infections by HCV belonging to genotype 1 or 2, the most medically important genotypes worldwide. (HEPATOLOGY 2005;42:1055–1062.)

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