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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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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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.
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Norman M. Kneteman is an officer and stockholder with KMT Hepatech, Inc., which owns the SCID/uPA chimeric mouse model.
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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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DOI: https://doi.org/10.1038/nm1698
