Occludin-binding single-chain variable fragment and antigen-binding fragment antibodies prevent hepatitis C virus infection

FEBS Lett. 2021 Jan;595(2):220-229. doi: 10.1002/1873-3468.13975. Epub 2020 Nov 7.

Abstract

Occludin (OCLN) is a tetraspan membrane component of epithelial tight junctions and a known receptor for hepatitis C virus (HCV). Previously, we established functional monoclonal antibodies (mAbs) that bind to each extracellular loop of OCLN and showed their ability to prevent in vitro and in vivo HCV infection. In this study, we converted these mAbs to corresponding monovalent antigen-binding fragments (Fabs) and single-chain variable fragment (scFv) antibodies. These Fab fragments and scFv antibodies demonstrate similar binding specificity and affinity to parental anti-OCLN mAbs. Moreover, Fab fragments and scFv antibodies inhibit in vitro HCV infection. The small functional monovalent OCLN-binding probes reported in our study have high potential as drug candidates and tools for biological and pharmaceutical studies of OCLN.

Keywords: antigen-binding fragments; hepatitis C virus; monoclonal antibody; occludin; single-chain antibody; tight junction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibody Affinity
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology
  • Cell Line
  • Hepacivirus / drug effects
  • Hepacivirus / physiology*
  • Hepatitis C / metabolism*
  • Hepatitis C / prevention & control
  • Humans
  • Immunoglobulin Fab Fragments / chemistry
  • Immunoglobulin Fab Fragments / pharmacology*
  • Models, Biological
  • Occludin / chemistry
  • Occludin / metabolism*
  • Single-Chain Antibodies / chemistry
  • Single-Chain Antibodies / pharmacology*
  • Virus Internalization / drug effects
  • Virus Replication / drug effects

Substances

  • Antiviral Agents
  • Immunoglobulin Fab Fragments
  • OCLN protein, human
  • Occludin
  • Single-Chain Antibodies