Antibody Repertoire Analysis of Hepatitis C Virus Infections Identifies Immune Signatures Associated With Spontaneous Clearance
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 chron...
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doaj-efa7cf7906384b49962a86e003a8452f2020-11-24T23:26:36ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-12-01910.3389/fimmu.2018.03004421638Antibody Repertoire Analysis of Hepatitis C Virus Infections Identifies Immune Signatures Associated With Spontaneous ClearanceSivan Eliyahu0Oz Sharabi1Shiri Elmedvi2Reut Timor3Ateret Davidovich4Francois Vigneault5Chris Clouser6Ronen Hope7Assy Nimer8Marius Braun9Yaacov Y. Weiss10Pazit Polak11Gur Yaari12Meital Gal-Tanamy13Molecular Virology Lab, The Azrieli Faculty of Medicine, Bar-Ilan University, Safed, IsraelBioengineering, Faculty of Engineering, Bar-Ilan University, Ramat-Gan, IsraelMolecular Virology Lab, The Azrieli Faculty of Medicine, Bar-Ilan University, Safed, IsraelBioengineering, Faculty of Engineering, Bar-Ilan University, Ramat-Gan, IsraelMolecular Virology Lab, The Azrieli Faculty of Medicine, Bar-Ilan University, Safed, IsraelAbVitro, Inc., Boston, MA, United StatesAbVitro, Inc., Boston, MA, United StatesBioengineering, Faculty of Engineering, Bar-Ilan University, Ramat-Gan, IsraelInternal Medicine Department A, Western Galilee Medical Center, Naharyia and Faculty of Medicine in the Galilee, Bar-Ilan University, Safed, IsraelLiver Institute, Rabin Medical Center, Sackler School of Medicine, Tel-Aviv University, Tel Aviv-Yafo, IsraelBioengineering, Faculty of Engineering, Bar-Ilan University, Ramat-Gan, IsraelBioengineering, Faculty of Engineering, Bar-Ilan University, Ramat-Gan, IsraelBioengineering, Faculty of Engineering, Bar-Ilan University, Ramat-Gan, IsraelMolecular Virology Lab, The Azrieli Faculty of Medicine, Bar-Ilan University, Safed, IsraelHepatitis 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, ~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 clusters 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.https://www.frontiersin.org/article/10.3389/fimmu.2018.03004/fullhepatitis C virusantibody repertoireneutralizing antibodiesinfectious diseaseimmune signature |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Sivan Eliyahu Oz Sharabi Shiri Elmedvi Reut Timor Ateret Davidovich Francois Vigneault Chris Clouser Ronen Hope Assy Nimer Marius Braun Yaacov Y. Weiss Pazit Polak Gur Yaari Meital Gal-Tanamy |
spellingShingle |
Sivan Eliyahu Oz Sharabi Shiri Elmedvi Reut Timor Ateret Davidovich Francois Vigneault Chris Clouser Ronen Hope Assy Nimer Marius Braun Yaacov Y. Weiss Pazit Polak Gur Yaari Meital Gal-Tanamy Antibody Repertoire Analysis of Hepatitis C Virus Infections Identifies Immune Signatures Associated With Spontaneous Clearance Frontiers in Immunology hepatitis C virus antibody repertoire neutralizing antibodies infectious disease immune signature |
author_facet |
Sivan Eliyahu Oz Sharabi Shiri Elmedvi Reut Timor Ateret Davidovich Francois Vigneault Chris Clouser Ronen Hope Assy Nimer Marius Braun Yaacov Y. Weiss Pazit Polak Gur Yaari Meital Gal-Tanamy |
author_sort |
Sivan Eliyahu |
title |
Antibody Repertoire Analysis of Hepatitis C Virus Infections Identifies Immune Signatures Associated With Spontaneous Clearance |
title_short |
Antibody Repertoire Analysis of Hepatitis C Virus Infections Identifies Immune Signatures Associated With Spontaneous Clearance |
title_full |
Antibody Repertoire Analysis of Hepatitis C Virus Infections Identifies Immune Signatures Associated With Spontaneous Clearance |
title_fullStr |
Antibody Repertoire Analysis of Hepatitis C Virus Infections Identifies Immune Signatures Associated With Spontaneous Clearance |
title_full_unstemmed |
Antibody Repertoire Analysis of Hepatitis C Virus Infections Identifies Immune Signatures Associated With Spontaneous Clearance |
title_sort |
antibody repertoire analysis of hepatitis c virus infections identifies immune signatures associated with spontaneous clearance |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2018-12-01 |
description |
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, ~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 clusters 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. |
topic |
hepatitis C virus antibody repertoire neutralizing antibodies infectious disease immune signature |
url |
https://www.frontiersin.org/article/10.3389/fimmu.2018.03004/full |
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