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Title: Genetic and structural insights into broad neutralization of hepatitis C virus by human V H 1-69 antibodies

Abstract

An effective vaccine to the antigenically diverse hepatitis C virus (HCV) must target conserved immune epitopes. Here, we investigate cross-neutralization of HCV genotypes by broadly neutralizing antibodies (bNAbs) encoded by the relatively abundant human gene familyV H1-69. We have deciphered the molecular requirements for cross-neutralization by this unique class of human antibodies from crystal structures of HCV E2 in complex with bNAbs. An unusually high binding affinity is found for germ line–reverted versions of V H1-69 precursor antibodies, and neutralization breadth is acquired during affinity maturation. Deep sequencing analysis of an HCV-immune B cell repertoire further demonstrates the importance of theV H1-69gene family in the generation of HCV bNAbs. This study therefore provides critical insights into immune recognition of HCV with important implications for rational vaccine design.

Authors:
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Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
National Institutes of Health (NIH)
OSTI Identifier:
1502256
Resource Type:
Journal Article
Journal Name:
Science Advances
Additional Journal Information:
Journal Volume: 5; Journal Issue: 1; Journal ID: ISSN 2375-2548
Publisher:
AAAS
Country of Publication:
United States
Language:
ENGLISH

Citation Formats

Tzarum, Netanel, Giang, Erick, Kong, Leopold, He, Linling, Prentoe, Jannick, Augestad, Elias, Hua, Yuanzi, Castillo, Shaun, Lauer, Georg M., Bukh, Jens, Zhu, Jiang, Wilson, Ian A., and Law, Mansun. Genetic and structural insights into broad neutralization of hepatitis C virus by human V H 1-69 antibodies. United States: N. p., 2019. Web. doi:10.1126/sciadv.aav1882.
Tzarum, Netanel, Giang, Erick, Kong, Leopold, He, Linling, Prentoe, Jannick, Augestad, Elias, Hua, Yuanzi, Castillo, Shaun, Lauer, Georg M., Bukh, Jens, Zhu, Jiang, Wilson, Ian A., & Law, Mansun. Genetic and structural insights into broad neutralization of hepatitis C virus by human V H 1-69 antibodies. United States. doi:10.1126/sciadv.aav1882.
Tzarum, Netanel, Giang, Erick, Kong, Leopold, He, Linling, Prentoe, Jannick, Augestad, Elias, Hua, Yuanzi, Castillo, Shaun, Lauer, Georg M., Bukh, Jens, Zhu, Jiang, Wilson, Ian A., and Law, Mansun. Tue . "Genetic and structural insights into broad neutralization of hepatitis C virus by human V H 1-69 antibodies". United States. doi:10.1126/sciadv.aav1882.
@article{osti_1502256,
title = {Genetic and structural insights into broad neutralization of hepatitis C virus by human V H 1-69 antibodies},
author = {Tzarum, Netanel and Giang, Erick and Kong, Leopold and He, Linling and Prentoe, Jannick and Augestad, Elias and Hua, Yuanzi and Castillo, Shaun and Lauer, Georg M. and Bukh, Jens and Zhu, Jiang and Wilson, Ian A. and Law, Mansun},
abstractNote = {An effective vaccine to the antigenically diverse hepatitis C virus (HCV) must target conserved immune epitopes. Here, we investigate cross-neutralization of HCV genotypes by broadly neutralizing antibodies (bNAbs) encoded by the relatively abundant human gene familyVH1-69. We have deciphered the molecular requirements for cross-neutralization by this unique class of human antibodies from crystal structures of HCV E2 in complex with bNAbs. An unusually high binding affinity is found for germ line–reverted versions of VH1-69 precursor antibodies, and neutralization breadth is acquired during affinity maturation. Deep sequencing analysis of an HCV-immune B cell repertoire further demonstrates the importance of theVH1-69gene family in the generation of HCV bNAbs. This study therefore provides critical insights into immune recognition of HCV with important implications for rational vaccine design.},
doi = {10.1126/sciadv.aav1882},
journal = {Science Advances},
issn = {2375-2548},
number = 1,
volume = 5,
place = {United States},
year = {2019},
month = {1}
}