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).

Jin-Yong Noh,Seong-Su Yuk,In-Soo Choi,Seung-Yong Park,Joong-Bok Lee,Chang-Seon Song,Dong-Hun Lee,Sang-Won Lee,Jung-Hoon Kwon,Jae-Keun Park,Yongchang Cao

doi:10.1371/journal.pone.0162946

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.

Highlights

Pathogenic avian influenza (HPAI) and Newcastle disease (ND) are devastating diseases in poultry with mortality rates of up to 100% and are classified as OIE-listed diseases [1, PLOS ONE | DOI:10.1371/journal.pone.0162946 September 14, 2016virus-like particle (VLP) Vaccine Protects Chickens from Highly pathogenic avian influenza (HPAI) and ND with differentiating infected animals from vaccinated animals (DIVA)
HA, F/HA and matrix 1 (M1) proteins were detected by Western blot analysis (Fig 2A and 2B) and VLPs were detected by transmission electron microscopy (TEM) (Fig 2C)
Several bivalent vaccines against HPAI and ND viruses have been produced in forms of live attenuated vector vaccines, inactivated vaccines, and VLP vaccines [28,29,30,31]

Summary

Introduction

Pathogenic avian influenza (HPAI) and Newcastle disease (ND) are devastating diseases in poultry with mortality rates of up to 100% and are classified as OIE-listed diseases [1, PLOS ONE | DOI:10.1371/journal.pone.0162946 September 14, 2016. HPAIV and NDV have become endemic in the poultry of many countries in Southeast Asia and vaccination for both diseases are commonly used in these countries [8, 9] In these countries, differentiating infected animals from vaccinated animals (DIVA) is important to make virus surveillance easier. VLP vaccines produced by using the most prominent immunogenic proteins of viruses have been shown to elicit high protective efficacies against various viral pathogens [14,15,16]. These vaccines provide numerous advantages over conventional vaccines, including safety, immunogenicity, and multivalency. We evaluated its immunogenicity and protective efficacy in specific-pathogen-free (SPF) chickens and assessed DIVA-ability of VLP vaccines by using nucleoprotein (NP) coated ELISA test for HPAIV and Hemagglutination Inhibition (HI) test for NDV

Ethics statement

Results

Discussion