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

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

doi:10.1126/sciadv.aav1882

Title: Genetic and structural insights into broad neutralization of hepatitis C virus by human V_H1-69 antibodies

Journal Article · Wed Jan 02 00:00:00 EST 2019 · Science Advances

DOI:https://doi.org/10.1126/sciadv.aav1882· OSTI ID:1502256

Tzarum, Netanel ^[1]; Giang, Erick ^[1]; Kong, Leopold ^[1];

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^[2]; Hua, Yuanzi ^[1];

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The Scripps Research Inst., La Jolla, CA (United States)
Univ. of Copenhagen (Denmark)
Massachusetts General Hospital and Harvard Medical School, Boston, MA (United States)

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_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 the V_H1-69 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.

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Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES); USDOE Office of Science (SC), Biological and Environmental Research (BER); National Institutes of Health (NIH)

Grant/Contract Number:: AC02-06CH11357; R01AI079031; R01AI123365; R01AI106005; U19AI123861; U01AI131314; R01AI129698; P01AI124337

OSTI ID:: 1502256

Journal Information:: Science Advances, Vol. 5, Issue 1; ISSN 2375-2548

Publisher:: AAASCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

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Cited by: 52 works

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