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

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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.

In: Science Advances, Vol. 5, No. 1, eaav1882, 2019.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Tzarum, N, Giang, E, Kong, L, He, L, Prentoe, J, Augestad, E, Hua, Y, Castillo, S, Lauer, GM, Bukh, J, Zhu, J, Wilson, IA & Law, M 2019, 'Genetic and structural insights into broad neutralization of hepatitis C virus by human VH1-69 antibodies', Science Advances, vol. 5, no. 1, eaav1882. https://doi.org/10.1126/sciadv.aav1882

APA

Tzarum, N., Giang, E., Kong, L., He, L., Prentoe, J., Augestad, E., Hua, Y., Castillo, S., Lauer, G. M., Bukh, J., Zhu, J., Wilson, I. A., & Law, M. (2019). Genetic and structural insights into broad neutralization of hepatitis C virus by human VH1-69 antibodies. Science Advances, 5(1), [eaav1882]. https://doi.org/10.1126/sciadv.aav1882

Vancouver

Tzarum N, Giang E, Kong L, He L, Prentoe J, Augestad E et al. Genetic and structural insights into broad neutralization of hepatitis C virus by human VH1-69 antibodies. Science Advances. 2019;5(1). eaav1882. https://doi.org/10.1126/sciadv.aav1882

Author

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 VH1-69 antibodies. In: Science Advances. 2019 ; Vol. 5, No. 1.

Bibtex

@article{17a2bd09645d4500b51a2a855921c63d,
title = "Genetic and structural insights into broad neutralization of hepatitis C virus by human VH1-69 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 family VH1-69. 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 VH1-69 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.",
author = "Netanel Tzarum and Erick Giang and Leopold Kong and Linling He and Jannick Prentoe and Elias Augestad and Yuanzi Hua and Shaun Castillo and Lauer, {Georg M.} and Jens Bukh and Jiang Zhu and Wilson, {Ian A.} and Mansun Law",
year = "2019",
doi = "10.1126/sciadv.aav1882",
language = "English",
volume = "5",
journal = "Science advances",
issn = "2375-2548",
publisher = "American Association for the Advancement of Science",
number = "1",

}

RIS

TY - JOUR

T1 - Genetic and structural insights into broad neutralization of hepatitis C virus by human VH1-69 antibodies

AU - Tzarum, Netanel

AU - Giang, Erick

AU - Kong, Leopold

AU - He, Linling

AU - Prentoe, Jannick

AU - Augestad, Elias

AU - Hua, Yuanzi

AU - Castillo, Shaun

AU - Lauer, Georg M.

AU - Bukh, Jens

AU - Zhu, Jiang

AU - Wilson, Ian A.

AU - Law, Mansun

PY - 2019

Y1 - 2019

N2 - 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 VH1-69. 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 VH1-69 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.

AB - 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 VH1-69. 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 VH1-69 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.

U2 - 10.1126/sciadv.aav1882

DO - 10.1126/sciadv.aav1882

M3 - Journal article

C2 - 30613781

AN - SCOPUS:85059500706

VL - 5

JO - Science advances

JF - Science advances

SN - 2375-2548

IS - 1

M1 - eaav1882

ER -

ID: 212852952