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 journal › Journal article › Research › peer-review
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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