A novel monoclonal anti-CD81 antibody produced by genetic immunization efficiently inhibits Hepatitis C virus cell-cell transmission

PLoS One. 2013 May 21;8(5):e64221. doi: 10.1371/journal.pone.0064221. Print 2013.

Abstract

Background and aims: Hepatitis C virus (HCV) infection is a challenge to prevent and treat because of the rapid development of drug resistance and escape. Viral entry is required for initiation, spread, and maintenance of infection, making it an attractive target for antiviral strategies.

Methods: Using genetic immunization, we produced four monoclonal antibodies (mAbs) against the HCV host entry factor CD81. The effects of antibodies on inhibition of HCV infection and dissemination were analyzed in HCV permissive human liver cell lines.

Results: The anti-CD81 mAbs efficiently inhibited infection by HCV of different genotypes as well as a HCV escape variant selected during liver transplantation and re-infecting the liver graft. Kinetic studies indicated that anti-CD81 mAbs target a post-binding step during HCV entry. In addition to inhibiting cell-free HCV infection, one antibody was also able to block neutralizing antibody-resistant HCV cell-cell transmission and viral dissemination without displaying any detectable toxicity.

Conclusion: A novel anti-CD81 mAb generated by genetic immunization efficiently blocks HCV spread and dissemination. This antibody will be useful to further unravel the role of virus-host interactions during HCV entry and cell-cell transmission. Furthermore, this antibody may be of interest for the development of antivirals for prevention and treatment of HCV infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology*
  • Antibodies, Neutralizing / immunology
  • Cell Membrane / immunology
  • Hepacivirus / immunology*
  • Hepacivirus / physiology*
  • Hepatitis C / immunology
  • Hepatitis C / virology
  • Hepatitis C Antibodies / immunology*
  • Humans
  • Immunization*
  • Rats
  • Rats, Wistar
  • Tetraspanin 28 / immunology*
  • Viral Envelope Proteins / immunology
  • Virus Internalization*

Substances

  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • Hepatitis C Antibodies
  • Tetraspanin 28
  • Viral Envelope Proteins

Grants and funding

This work was supported by Inserm, University of Strasbourg, the European Union (ERC-2008-AdG-233130-HEPCENT, INTERREG-IV-Rhin Supérieur-FEDER-Hepato-Regio-Net 2009 and 2012), the chair of excellence program of the Agence Nationale de la Recherche France (ANR-05-CEXC-008), ANRS (2009/183, 2011/132, 2012/239), Laboratoire d'excellence LabEx HEPSYS (Investissement d'Avenir; ANR-10-LAB-28), the Direction Générale de l'Offre de Soins (A12027MS) and Aldevron (Pro Inno II (KA0690901UL8)). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.