Broadly Neutralizing Antibody Mediated Clearance of Human Hepatitis C Virus Infection.

Kinchen VJ, Zahid MN, Flyak AI, Soliman MG, Learn GH, Wang S, Davidson E, Doranz BJ, Ray SC, Cox AL, Crowe JE, Bjorkman PJ, Shaw GM, Bailey JR
Cell Host Microbe. 2018 24 (5): 717-730.e5

PMID: 30439341 · PMCID: PMC6250073 · DOI:10.1016/j.chom.2018.10.012

The role that broadly neutralizing antibodies (bNAbs) play in natural clearance of human hepatitis C virus (HCV) infection and the underlying mechanisms remain unknown. Here, we investigate the mechanism by which bNAbs, isolated from two humans who spontaneously cleared HCV infection, contribute to HCV control. Using viral gene sequences amplified from longitudinal plasma of the two subjects, we found that these bNAbs, which target the front layer of the HCV envelope protein E2, neutralized most autologous HCV strains. Acquisition of resistance to bNAbs by some autologous strains was accompanied by progressive loss of E2 protein function, and temporally associated with HCV clearance. These data demonstrate that bNAbs can mediate clearance of human HCV infection by neutralizing infecting strains and driving escaped viruses to an unfit state. These immunopathologic events distinguish HCV from HIV-1 and suggest that development of an HCV vaccine may be achievable.

Copyright © 2018 Elsevier Inc. All rights reserved.

MeSH Terms (22)

Animals Antibodies, Monoclonal Antibodies, Neutralizing Antibody Specificity Base Sequence Binding Sites Cell Line Cricetulus Epitopes Female HEK293 Cells Hepacivirus Hepatitis C Hepatitis C Antibodies HIV-1 Humans Immunologic Memory Male Models, Molecular Mutagenesis, Site-Directed Viral Envelope Proteins Viral Load

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