Sustained E2 antibody response correlates with reduced peak viremia after hepatitis C virus infection in the chimpanzee

Authors

  • Jin-Won Youn,

    1. National Research Laboratory of DNA Medicine, Division of Molecular and Life Science, POSTECH Biotech Center, Pohang University of Science and Technology, Pohang, Republic of Korea
    2. The Laboratory of Virology, the Lindsley F. Kimball Research Institute of the New York Blood Center, New York, NY
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    • J.-W.Y. and S.-H.P. contributed equally to this work.

  • Su-Hyung Park,

    1. National Research Laboratory of DNA Medicine, Division of Molecular and Life Science, POSTECH Biotech Center, Pohang University of Science and Technology, Pohang, Republic of Korea
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    • J.-W.Y. and S.-H.P. contributed equally to this work.

  • Dimitri Lavillette,

    1. Laboratoire de Vectorologie Retrovirale et Therapie Genique, INSERM U412/IFR128 BioSciences Lyon-Gerland, ENS de Lyon, Lyon, France
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  • Francois-Loic Cosset,

    1. Laboratoire de Vectorologie Retrovirale et Therapie Genique, INSERM U412/IFR128 BioSciences Lyon-Gerland, ENS de Lyon, Lyon, France
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  • Se-Hwan Yang,

    1. National Research Laboratory of DNA Medicine, Division of Molecular and Life Science, POSTECH Biotech Center, Pohang University of Science and Technology, Pohang, Republic of Korea
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  • Chang Geun Lee,

    1. National Research Laboratory of DNA Medicine, Division of Molecular and Life Science, POSTECH Biotech Center, Pohang University of Science and Technology, Pohang, Republic of Korea
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  • Hyun-Tak Jin,

    1. National Research Laboratory of DNA Medicine, Division of Molecular and Life Science, POSTECH Biotech Center, Pohang University of Science and Technology, Pohang, Republic of Korea
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  • Chang-Min Kim,

    1. Research Institute, National Cancer Center, Goyang, Republic of Korea
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  • Mohamed Tarek M. Shata,

    1. Viral Immunology Laboratory, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH
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  • Dong-Hun Lee,

    1. The Laboratory of Virology, the Lindsley F. Kimball Research Institute of the New York Blood Center, New York, NY
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  • Wolfram Pfahler,

    1. The Laboratory of Virology, the Lindsley F. Kimball Research Institute of the New York Blood Center, New York, NY
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  • Alfred M. Prince,

    1. The Laboratory of Virology, the Lindsley F. Kimball Research Institute of the New York Blood Center, New York, NY
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  • Young Chul Sung

    Corresponding author
    1. National Research Laboratory of DNA Medicine, Division of Molecular and Life Science, POSTECH Biotech Center, Pohang University of Science and Technology, Pohang, Republic of Korea
    • Division of Molecular and Life Sciences, POSTECH Biotech Center, Pohang University of Science and Technology, San 31, Hyojadong, Namgu, Pohang, 790-784, Republic of Korea
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    • fax: (82) 54-279-5544


  • Potential conflict of interest: Nothing to report.

Abstract

Immune correlates of protection against hepatitis C virus (HCV) infection are not well understood. Here we investigated 2 naive and 6 immunized chimpanzees before and after intravenous challenge, 12 weeks after the last immunization, with 100 50% chimpanzee infectious doses (CID50) of heterologous genotype 1b HCV. Vaccination with recombinant DNA and adenovirus vaccines expressing HCV core, E1E2, and NS3-5 genes induced long-term HCV-specific antibody and T-cell responses and reduced peak viral load about 100 times compared with controls (5.91 ± 0.38 vs. 3.81 ± 0.71 logs, respectively). There was a statistically significant inverse correlation between peak viral loads and envelope glycoprotein 2 (E2)-specific antibody responses at the time of challenge. Interestingly, one vaccinee that had sterilizing immunity against slightly heterologous virus generated the highest level of E2-specific total and neutralizing antibody responses as well as strong NS3/NS5-specific T-cell proliferative responses. The other four vaccinees with low levels of E2-specific antibody had about 44-fold reduced peak viral loads but eventually developed persistent infections. In conclusion, vaccine-induced E2-specific antibody plays an important role in prevention from nonhomologous virus infection and may provide new insight into the development of an effective HCV vaccine. (HEPATOLOGY 2005;42:1429–1436.)

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