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Cell Host Microbe. 2018 Nov 14;24(5):717-730.e5. doi: 10.1016/j.chom.2018.10.012.

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

Author information

1
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
2
Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Microbiology, University of Pennsylvania, Philadelphia, PA 19104, USA.
3
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
4
Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
5
Integral Molecular, Inc., Philadelphia, PA 19104, USA.
6
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
7
Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
8
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address: jbailey7@jhmi.edu.

Abstract

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.

KEYWORDS:

HCV clearance; antibody specificity; binding sites; hepatitis C virus; immunologic memory; neutralizing antibodies

PMID:
30439341
PMCID:
PMC6250073
[Available on 2019-11-14]
DOI:
10.1016/j.chom.2018.10.012

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