Chimeric Bivalent Virus-Like Particle Vaccine for H5N1 HPAI and ND Confers Protection against a Lethal Challenge in Chickens and Allows a Strategy of Differentiating Infected from Vaccinated Animals (DIVA)

PLoS One. 2016 Sep 14;11(9):e0162946. doi: 10.1371/journal.pone.0162946. eCollection 2016.

Abstract

Highly pathogenic avian influenza (HPAI) and Newcastle disease (ND) are considered as the most devastating poultry infections, owing to their worldwide distribution and economical threat. Vaccines have been widely used to control these diseases in the poultry industry in endemic countries. However, vaccination policy without differentiating infected animals from vaccinated animals (DIVA) makes the virus surveillance difficult. In this study, we developed a bivalent virus-like particle (VLP) vaccine that is composed of the hemagglutinin (HA) and matrix 1 (M1) proteins of the H5N1 HPAI virus (HPAIV) and a chimeric protein containing the ectodomain of the ND virus (NDV) fusion (F) protein fused with the cytoplasmic and transmembrane domains of the HPAIV HA protein. A single immunization of chickens with the chimeric VLP vaccine induced high levels of hemagglutination inhibition (HI) antibody titers against H5N1 HPAI virus and anti-NDV antibody detected in ELISA and protected chickens against subsequent lethal HPAIV and NDV infections. Furthermore, we could easily perform DIVA test using the commercial NP-cELISA tests against HPAIV and HI assay against NDV. These results strongly suggest that utilization of chimeric VLP vaccine in poultry species would be a promising strategy for the better control of HPAI and ND simultaneously.

MeSH terms

  • Animals
  • Chickens / immunology
  • Chickens / virology
  • Cloning, Molecular
  • Influenza A Virus, H5N1 Subtype / immunology*
  • Influenza Vaccines / immunology
  • Influenza Vaccines / therapeutic use*
  • Influenza in Birds / immunology
  • Influenza in Birds / prevention & control*
  • Influenza in Birds / virology
  • Microscopy, Electron
  • Newcastle Disease / immunology
  • Newcastle Disease / prevention & control*
  • Newcastle disease virus / immunology
  • Recombinant Fusion Proteins / immunology
  • Recombinant Fusion Proteins / therapeutic use
  • Vaccines, Combined / immunology
  • Vaccines, Combined / therapeutic use*
  • Vaccines, Virus-Like Particle / immunology
  • Vaccines, Virus-Like Particle / therapeutic use*

Substances

  • Influenza Vaccines
  • Recombinant Fusion Proteins
  • Vaccines, Combined
  • Vaccines, Virus-Like Particle

Grants and funding

This research was supported by the Animal Disease Management Technology Development Program (Grant No. 313013-3), Ministry of Agriculture, Food, and Rural Affairs, Republic of Korea. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.