Prevention of hepatitis C virus infection in chimpanzees by hyperimmune serum against the hypervariable region 1 of the envelope 2 protein

  • Patrizia Farci
    Hepatitis Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; SmithKline Beecham Biologicals, B-1330 Rixensart, Belgium; Istituto di Medicina Interna, University of Cagliari, 09124 Cagliari, Italy; Department of Bacteriology, University of Tokyo, Tokyo 113, Japan; Bioqual Inc., Rockville, MD 20852; and Department of Transfusion Medicine, Warren G. Magnuson Clinical Center, National ...
  • Atsushi Shimoda
    Hepatitis Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; SmithKline Beecham Biologicals, B-1330 Rixensart, Belgium; Istituto di Medicina Interna, University of Cagliari, 09124 Cagliari, Italy; Department of Bacteriology, University of Tokyo, Tokyo 113, Japan; Bioqual Inc., Rockville, MD 20852; and Department of Transfusion Medicine, Warren G. Magnuson Clinical Center, National ...
  • Doris Wong
    Hepatitis Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; SmithKline Beecham Biologicals, B-1330 Rixensart, Belgium; Istituto di Medicina Interna, University of Cagliari, 09124 Cagliari, Italy; Department of Bacteriology, University of Tokyo, Tokyo 113, Japan; Bioqual Inc., Rockville, MD 20852; and Department of Transfusion Medicine, Warren G. Magnuson Clinical Center, National ...
  • Teresa Cabezon
    Hepatitis Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; SmithKline Beecham Biologicals, B-1330 Rixensart, Belgium; Istituto di Medicina Interna, University of Cagliari, 09124 Cagliari, Italy; Department of Bacteriology, University of Tokyo, Tokyo 113, Japan; Bioqual Inc., Rockville, MD 20852; and Department of Transfusion Medicine, Warren G. Magnuson Clinical Center, National ...
  • Daniela De Gioannis
    Hepatitis Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; SmithKline Beecham Biologicals, B-1330 Rixensart, Belgium; Istituto di Medicina Interna, University of Cagliari, 09124 Cagliari, Italy; Department of Bacteriology, University of Tokyo, Tokyo 113, Japan; Bioqual Inc., Rockville, MD 20852; and Department of Transfusion Medicine, Warren G. Magnuson Clinical Center, National ...
  • Antonello Strazzera
    Hepatitis Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; SmithKline Beecham Biologicals, B-1330 Rixensart, Belgium; Istituto di Medicina Interna, University of Cagliari, 09124 Cagliari, Italy; Department of Bacteriology, University of Tokyo, Tokyo 113, Japan; Bioqual Inc., Rockville, MD 20852; and Department of Transfusion Medicine, Warren G. Magnuson Clinical Center, National ...
  • Yohko Shimizu
    Hepatitis Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; SmithKline Beecham Biologicals, B-1330 Rixensart, Belgium; Istituto di Medicina Interna, University of Cagliari, 09124 Cagliari, Italy; Department of Bacteriology, University of Tokyo, Tokyo 113, Japan; Bioqual Inc., Rockville, MD 20852; and Department of Transfusion Medicine, Warren G. Magnuson Clinical Center, National ...
  • Max Shapiro
    Hepatitis Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; SmithKline Beecham Biologicals, B-1330 Rixensart, Belgium; Istituto di Medicina Interna, University of Cagliari, 09124 Cagliari, Italy; Department of Bacteriology, University of Tokyo, Tokyo 113, Japan; Bioqual Inc., Rockville, MD 20852; and Department of Transfusion Medicine, Warren G. Magnuson Clinical Center, National ...
  • Harvey J. Alter
    Hepatitis Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; SmithKline Beecham Biologicals, B-1330 Rixensart, Belgium; Istituto di Medicina Interna, University of Cagliari, 09124 Cagliari, Italy; Department of Bacteriology, University of Tokyo, Tokyo 113, Japan; Bioqual Inc., Rockville, MD 20852; and Department of Transfusion Medicine, Warren G. Magnuson Clinical Center, National ...
  • Robert H. Purcell
    Hepatitis Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; SmithKline Beecham Biologicals, B-1330 Rixensart, Belgium; Istituto di Medicina Interna, University of Cagliari, 09124 Cagliari, Italy; Department of Bacteriology, University of Tokyo, Tokyo 113, Japan; Bioqual Inc., Rockville, MD 20852; and Department of Transfusion Medicine, Warren G. Magnuson Clinical Center, National ...

抄録

<jats:p> The identification of the neutralization domains of hepatitis C virus (HCV) is essential for the development of an effective vaccine. Here, we show that the hypervariable region 1 (HVR1) of the envelope 2 (E2) protein is a critical neutralization domain of HCV. Neutralization of HCV <jats:italic>in vitro</jats:italic> was attempted with a rabbit hyperimmune serum raised against a homologous synthetic peptide derived from the HVR1 of the E2 protein, and the residual infectivity was evaluated by inoculation of HCV-seronegative chimpanzees. The source of HCV was plasma obtained from a patient (H) during the acute phase of posttransfusion non-A, non-B hepatitis, which had been titered for infectivity in chimpanzees. The anti-HVR1 antiserum induced protection against homologous HCV infection in chimpanzees, but not against the emergence of neutralization escape mutants that were found to be already present in the complex viral quasispecies of the inoculum. The finding that HVR1 can elicit protective immunity opens new perspectives for the development of effective preventive strategies. However, the identification of the most variable region of HCV as a critical neutralization domain poses a major challenge for the development of a broadly reactive vaccine against HCV. </jats:p>

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