Human single-chain antibodies that neutralize homologous and heterologous strains and clades of influenza A virus subtype H5N1

Antivir Ther. 2009;14(2):221-30.

Abstract

Background: Human antibodies that interfere with the biological activity of haemagglutinins (HAs) of influenza viruses have high potential as an antiviral agent.

Methods: Human single-chain antibody fragments (HuScFv) to recombinant and native HAs of the influenza virus H5N1 subtype were produced using a human antibody phage display library with the intention to increase the therapeutic arsenal against this highly pathogenic virus.

Results: The HuScFv inhibited HA activity and neutralized infectivity of both homologous and heterologous strains and clades of the H5N1 subtype in Madin-Darby canine kidney cell cultures. Intraperitoneally injected HuScFv also mediated immunotherapeutic protection in mice that were intranasally challenged with highly pathogenic H5N1 viruses belonging to different strains and clades.

Conclusions: Our data indicate that it might be worth pursuing these HuScFv further for future consideration as candidates for influenza intervention and treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Viral / administration & dosage*
  • Cell Line
  • Dogs
  • Hemagglutinin Glycoproteins, Influenza Virus / immunology
  • Humans
  • Immunization, Passive
  • Immunoglobulin Fragments / administration & dosage
  • Immunologic Factors / administration & dosage
  • Influenza A Virus, H5N1 Subtype* / drug effects
  • Influenza A Virus, H5N1 Subtype* / immunology
  • Influenza, Human / therapy*
  • Injections, Intraperitoneal
  • Mice

Substances

  • Antibodies, Monoclonal
  • Antibodies, Viral
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Immunoglobulin Fragments
  • Immunologic Factors