Passive immunization with a recombinant adenovirus expressing an HA (H5)-specific single-domain antibody protects mice from lethal influenza infection

Antiviral Res. 2013 Mar;97(3):318-28. doi: 10.1016/j.antiviral.2012.12.021. Epub 2012 Dec 26.

Abstract

One effective method for the prevention and treatment of influenza infection is passive immunization. In our study, we examined the feasibility of creating an antibody-based preparation with a prolonged protective effect against influenza virus. Single-domain antibodies (sdAbs) specific for influenza virus hemagglutinin were generated. Experiments in mouse models showed 100% survivability for both intranasal sdAbs administration 24h prior to influenza challenge and 24h after infection. sdAb-gene delivery by an adenoviral vector led to gene expression for up to 14days. Protection by a recombinant adenovirus containing the sdAb gene was observed in cases of administration prior to influenza infection (14d-24h). We also demonstrated that the single administration of a combined preparation containing sdAb DNA and protein expanded the protection time window from 14d prior to 48h after influenza infection. This approach and the application of a broad-spectrum sdAbs will allow the development of efficient drugs for the prevention and treatment of viral infections produced by pandemic virus variants and other infections.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Adenoviridae / immunology
  • Animals
  • Antibodies, Viral / genetics*
  • Antibodies, Viral / immunology*
  • Cell Line
  • Female
  • Genetic Vectors / genetics
  • Genetic Vectors / immunology
  • Hemagglutinin Glycoproteins, Influenza Virus / immunology*
  • Humans
  • Immunization, Passive
  • Influenza A Virus, H5N2 Subtype / genetics
  • Influenza A Virus, H5N2 Subtype / immunology*
  • Influenza, Human / immunology
  • Influenza, Human / prevention & control*
  • Influenza, Human / virology
  • Mice
  • Mice, Inbred BALB C
  • Single-Domain Antibodies / genetics*
  • Single-Domain Antibodies / immunology*

Substances

  • Antibodies, Viral
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Single-Domain Antibodies