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Broadly neutralizing antibodies protect against hepatitis C virus quasispecies challenge

Nature Medicine volume 14, pages 25–27 (2008)Cite this article

Abstract

A major problem in hepatitis C virus (HCV) immunotherapy or vaccine design is the extreme variability of the virus. We identified human monoclonal antibodies (mAbs) that neutralize genetically diverse HCV isolates and protect against heterologous HCV quasispecies challenge in a human liver–chimeric mouse model. The results provide evidence that broadly neutralizing antibodies to HCV protect against heterologous viral infection and suggest that a prophylactic vaccine against HCV may be achievable.

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Figure 1: E2-specific human mAbs.

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Acknowledgements

M.L. was an Elizabeth Glaser Pediatric AIDS Foundation Scholar. T.M. was supported in part by the Sjögren's Syndrome Foundation and Arthritis Foundation. N.M.K. was supported by a Senior Scholar award from the Alberta Heritage Foundation for Medical Research and a Wyeth Canada–Canadian Institutes for Health Research Clinical Research Chair in Transplantation. We thank A. Hessell for help in antibody production and P. Poignard for discussion. We acknowledge the generous gifts of J. Dubuisson (Institut Pasteur de Lille; mAbs A4 and H53), A. Patel (University of Glasgow; mAbs AP33, AP320 and ALP98), S. Foung (Stanford University; mAbs CBH-2, CBH-5, CBH-4B and CBH-7), S. Levy (Stanford University; GST-CD81-LEL), T. Wakita (Tokyo Metropolitan Institute for Neuroscience; JFH-1 cDNA) and J. Bukh (US National Institutes of Health; H77 and J6 cDNA). This is article 18887 from The Scripps Research Institute.

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Author notes

  1. Toshiaki Maruyama

    Present address: Present address: Calmune Corporation, Suite 130, 9393 Towne Center Drive, San Diego, California 92121, USA.,

Authors and Affiliations

  1. Department of Immunology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, 92037, California, USA

    Mansun Law, Toshiaki Maruyama, Erick Giang & Dennis R Burton

  2. Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, 92037, California, USA

    Dennis R Burton

  3. Departments of Molecular and Experimental Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, 92037, California, USA

    Pablo Gastaminza & Francis V Chisari

  4. Department of Surgery, University of Alberta, 2-75 Heritage Medical Research Building, 114 Street and 87 Avenue, Edmonton, T6G 2S2, Alberta, Canada

    Jamie Lewis & Norman M Kneteman

  5. Institute of Infection, Immunity and Inflammation, School of Molecular Medical Sciences, the University of Nottingham, Queen's Medical Centre, Nottingham, NG7 2UH, UK

    Alexander W Tarr & Jonathan K Ball

  6. Division of Immunity and Infection, Institute of Biomedical Research, Medical School, University of Birmingham, Birmingham, B15 2TT, UK

    Zania Stamataki & Jane A McKeating

  7. School of Biological Sciences, University of Reading, Whiteknights, Reading, RG6 6AH, UK

    Ian M Jones

  8. Rheumatology Clinic, Scripps Memorial Hospital, 9850 Genesee Avenue #910, La Jolla, 92037, California, USA

    Robert I Fox

Authors
  1. Mansun Law
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  12. Jane A McKeating
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Contributions

M.L., N.M.K. and D.R.B. wrote the paper. T.M., R.I.F. and I.M.J. generated and panned the phage-display antibody library. M.L., E.G, Z.S, P.G., F.V.C. and J.A.M. performed the virus neutralization experiments and M.L., T.M., E.G., A.W.T. and J.K.B. performed the epitope mapping experiments. The mouse experiments and quantitative PCR were conducted by J.L. and N.M.K. and the downstream immunological and virus neutralization assays were performed by M.L. and E.G.

Corresponding authors

Correspondence to Norman M Kneteman or Dennis R Burton.

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Competing interests

Norman M. Kneteman is an officer and stockholder with KMT Hepatech, Inc., which owns the SCID/uPA chimeric mouse model.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–8 and Supplementary Methods (PDF 369 kb)

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Law, M., Maruyama, T., Lewis, J. et al. Broadly neutralizing antibodies protect against hepatitis C virus quasispecies challenge. Nat Med 14, 25–27 (2008). https://doi.org/10.1038/nm1698

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