An avian influenza H5N1 virus vaccine candidate based on the extracellular domain produced in yeast system as subviral particles protects chickens from lethal challenge

Antiviral Res. 2016 Sep;133:242-9. doi: 10.1016/j.antiviral.2016.08.001. Epub 2016 Aug 3.


Highly pathogenic avian influenza is an on-going problem in poultry and a potential human pandemic threat. Pandemics occur suddenly and vaccine production must be fast and effective to be of value in controlling the spread of the virus. In this study we evaluated the potential of a recombinant protein from the extracellular domain of an H5 hemagglutinin protein produced in a yeast expression system to act as an effective vaccine. Protein production was efficient, with up to 200 mg purified from 1 L of culture medium. We showed that the deletion of the multibasic cleavage site from the protein improves oligomerization and, consequentially, its immunogenicity. We also showed that immunization with this deleted protein protected chickens from challenge with a highly pathogenic avian influenza H5N1 virus. Our results suggest that this recombinant protein produced in yeast may be an effective vaccine against H5N1 virus in poultry.

Keywords: Avian influenza; H5N1; Pichia pastoris; Recombinant hemagglutinin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Viral / chemistry
  • Antigens, Viral / immunology*
  • Antigens, Viral / isolation & purification
  • Chickens*
  • Hemagglutinin Glycoproteins, Influenza Virus / chemistry
  • Hemagglutinin Glycoproteins, Influenza Virus / immunology
  • Influenza A Virus, H5N1 Subtype / genetics
  • Influenza A Virus, H5N1 Subtype / immunology*
  • Influenza Vaccines / immunology*
  • Influenza in Birds / mortality
  • Influenza in Birds / prevention & control*
  • Influenza in Birds / virology
  • Models, Molecular
  • Protein Conformation
  • Protein Interaction Domains and Motifs / immunology*
  • Protein Multimerization
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / immunology
  • Recombinant Proteins / isolation & purification
  • Recombinant Proteins / ultrastructure
  • Vaccines, Virus-Like Particle / immunology*
  • Vaccines, Virus-Like Particle / ultrastructure


  • Antigens, Viral
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Influenza Vaccines
  • Recombinant Proteins
  • Vaccines, Virus-Like Particle
  • hemagglutinin, avian influenza A virus