Genetic and structural insights into broad neutralization of hepatitis C virus by human VH1-69 antibodies

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 family V H 1-69. We have deciphered the...

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Bibliographic Details
Published in:Science advances 2019-01, Vol.5 (1), p.eaav1882-eaav1882
Main Authors: 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
Format: Article
Language:English
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60 APPLIED LIFE SCIENCES
SciAdv r-articles
Virology
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Summary: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 family V H 1-69. 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 the V H 1-69 gene 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.
ISSN:2375-2548
2375-2548
DOI:10.1126/sciadv.aav1882