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

SUBMITTER: Tzarum N 

PROVIDER: S-EPMC6314831 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature