Repertoire and Neutralizing Activity of Antibodies Against Hepatitis C Virus E2 Peptide in Patients With Spontaneous Resolution of Hepatitis C

J Infect Dis. 2019 Aug 30;220(7):1209-1218. doi: 10.1093/infdis/jiz274.

Abstract

Neutralizing antibodies can prevent hepatitis C virus (HCV) infection, one of the leading causes of cirrhosis and liver cancer. Here, we characterized the immunoglobulin repertoire of memory B-cell antibodies against a linear epitope in the central front layer of the HCV envelope (E2; amino acids 483-499) in patients who were infected in a single-source outbreak. A reverse transcription polymerase chain reaction-based immunoglobulin gene cloning and recombinant expression approach was used to express monoclonal antibodies from HCV E2 peptide-binding immunoglobulin G-positive memory B cells. We identified highly mutated antibodies with a neutralizing effect in vitro against different genotype isolates sharing similar gene features. Our data confirm the importance of VH1-69 use for neutralizing activity. The data offer a promising basis for vaccine research and the use of anti-E2 antibodies as a means of passive immunization.

Keywords: HCV; HCV envelope (E2) protein; anti-D cohort; memory B cells; neutralizing antibodies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal / immunology
  • B-Lymphocytes / immunology
  • Broadly Neutralizing Antibodies / immunology*
  • Cohort Studies
  • Epitopes, B-Lymphocyte / immunology*
  • Female
  • Genotype
  • HEK293 Cells
  • Hepacivirus / genetics
  • Hepacivirus / immunology*
  • Hepatitis C Antibodies / immunology*
  • Hepatitis C, Chronic / immunology*
  • Hepatitis C, Chronic / prevention & control
  • Hepatitis C, Chronic / virology
  • Humans
  • Immunoglobulin G / immunology*
  • Immunologic Memory
  • Male
  • Middle Aged
  • Rho(D) Immune Globulin / immunology
  • Single-Domain Antibodies / genetics
  • Viral Envelope Proteins / immunology*
  • Viral Hepatitis Vaccines / immunology

Substances

  • Antibodies, Monoclonal
  • Broadly Neutralizing Antibodies
  • Epitopes, B-Lymphocyte
  • Hepatitis C Antibodies
  • Immunoglobulin G
  • RHO(D) antibody
  • Rho(D) Immune Globulin
  • Single-Domain Antibodies
  • Viral Envelope Proteins
  • Viral Hepatitis Vaccines
  • glycoprotein E2, Hepatitis C virus