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Front. Immunol. | doi: 10.3389/fimmu.2018.03004

Antibody repertoire analysis of Hepatitis C virus infections identifies immune signatures associated with spontaneous clearance

 Sivan Eliyahu1, Oz Sharabi2,  Shiri Elmedvi1,  Reut Timor2, Ateret Davidovich1,  Francois Vigneault3, Chris Clouser3,  Ronen Hope2, Assy Nimer4, Marius Braun5, Yaacov Weiss2,  Pazit Polak2,  Gur Yaari2* and  Meital Gal Tanamy1*
  • 1Azrieli Faculty of Medicine, Israel
  • 2Bar-Ilan University, Israel
  • 3AbVitro, Inc., United States
  • 4Galilee Medical Center, Israel
  • 5Rabin Medical Center, Israel

Hepatitis C virus (HCV) is a major public health concern, with over 70 million people infected worldwide, who are at risk for developing life-threatening liver disease. No vaccine is available, and immunity against the virus is not well understood. Following the acute stage, HCV usually causes chronic infections. However, approximately 30% of infected individuals spontaneously clear the virus. Therefore, using HCV as a model for comparing immune responses between spontaneous clearer (SC) and chronically infected (CI) individuals may empower the identification of mechanisms governing viral infection outcomes. Here, we provide the first in-depth analysis of adaptive immune receptor repertoires in individuals with current or past HCV infection. We demonstrate that SC individuals, in contrast to CI patients, develop a cluster of antibodies with distinct properties. These antibodies’ characteristics were used in a machine learning framework to accurately predict infection outcome. Using combinatorial antibody phage display library technology, we identified HCV-specific antibody sequences. By integrating these data with the repertoire analysis, we constructed two antibodies characterized by high neutralization breadth, which are associated with clearance. This study provides insight into the nature of effective immune response against HCV and demonstrates an innovative approach for constructing antibodies correlating with successful infection clearance. It may have clinical implications for prognosis of the future status of infection, and the design of effective immunotherapies and a vaccine for HCV.

Keywords: Hepatits C virus, Antibody repertoire, neutralizing antibodies, Infectious Disease, Immune signature

Received: 29 Aug 2018; Accepted: 05 Dec 2018.

Edited by:

Deborah K. Dunn-Walters, University of Surrey, United Kingdom

Reviewed by:

Gregory C. Ippolito, University of Texas at Austin, United States
Christopher Sundling, Karolinska Institute (KI), Sweden  

Copyright: © 2018 Eliyahu, Sharabi, Elmedvi, Timor, Davidovich, Vigneault, Clouser, Hope, Nimer, Braun, Weiss, Polak, Yaari and Gal Tanamy. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Dr. Gur Yaari, Bar-Ilan University, Ramat Gan, 5290002, Tel Aviv District, Israel, gur.yaari@biu.ac.il
Dr. Meital Gal Tanamy, Azrieli Faculty of Medicine, Safed, 1311502, Israel, mgtanamy@gmail.com