JVI Accepts, published online ahead of print on 9 January 2008

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J. Virol. doi:10.1128/JVI.02252-07
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Increased CTL epitope variant cross-recognition and functional avidity are associated with HCV clearance

Daniel Yerly, David Heckerman, Todd M. Allen, John V. Chisholm III, Kellie Faircloth, Caitlyn H. Linde, Nicole Frahm, Joerg Timm, Werner J Pichler, Andreas Cerny, and Christian Brander

University of Bern, Clinic for Rheumatology and Clinical Immunology/Allergology, CH-3010 Bern, Switzerland; Massachusetts General Hospital and Harvard Medical School, Partners AIDS Research Center, Boston, MA, USA; Microsoft Research, Redmond, WA 98052, USA; University Hospital Essen, Institute for Virology, Essen, Germany, Ospedale Regionale di Lugano, Department of Medicine, CH-6903 Lugano, Switzerland

Hepatitis C Virus (HCV) clearance has been associated with reduced viral evolution in targeted CTL epitopes, suggesting that HCV clearers may mount CTL responses with a superior ability to recognize epitope variants and prevent viral immune escape. Here, 40 HCV-infected subjects were tested with 406 10mer peptides covering the vast majority of the sequence diversity spanning a 197 residues region of the NS3 protein. HCV clearers mounted significantly broader CTL responses of higher functional avidity and with wider variant cross-recognition capacity than non-clearers. These observations have important implications for vaccine approaches that may need to induce high avidity responses in-vivo.

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• Yerly, D., Heckerman, D., Allen, T., Suscovich, T. J., Jojic, N., Kadie, C., Pichler, W. J., Cerny, A., Brander, C. (2008). Design, Expression, and Processing of Epitomized Hepatitis C Virus-Encoded CTL Epitopes. J. Immunol. 181: 6361-6370 [Abstract] [Full Text]