Effect of fusion protein cleavage site sequence on generation of a genotype VII Newcastle disease virus vaccine.

Vinoth K Manoharan,Siba K Samal,Anandan Paldurai,Berin P Varghese,Charles J Russell

doi:10.1371/journal.pone.0197253

Abstract

Newcastle disease (ND) causes severe economic loss to poultry industry worldwide. Frequent outbreaks of ND in commercial chickens vaccinated with live vaccines suggest a need to develop improved vaccines that are genetically matched against circulating Newcastle disease virus (NDV) strains. In this study, the fusion protein cleavage site (FPCS) sequence of NDV strain Banjarmasin/010 (Banj), a genotype VII NDV, was individually modified using primer mutagenesis to those of avian paramyxovirus (APMV) serotypes 2, 7 and 8 and compared with the recombinant Banjarmasin (rBanj) with avirulent NDV LaSota cleavage site (rBanj-LaSota). These FPCS mutations changed the in vitro cell-to-cell fusion activity and made rBanj FPCS mutant viruses highly attenuated in chickens. When chickens immunized with the rBanj FPCS mutant viruses and challenged with the virulent Banj, there was reduced challenge virus shedding observed compared to chickens immunized with the heterologous vaccine strain LaSota. Among the genotype VII NDV Banj vaccine candidates, rBanj-LaSota and rBanj containing FPCS of APMV-8 induced highest neutralizing antibody titers and protected chickens with reduced challenge virus shedding. These results show the effect of the F protein cleavage site sequence in generating genotype VII matched NDV vaccines.

Highlights

Newcastle disease virus (NDV) causes a severe disease in chickens worldwide
The pathogenicity of recombinant Banjarmasin (rBanj) fusion protein cleavage site (FPCS) mutant viruses rBanj-LaSota, rBanj-APMV2, rBanj-APMV7 and rBanj-APMV8 were evaluated by intracerebral pathogenicity index (ICPI) test in 1-day-old SPF chicks [21]
The FPCS sequence of avirulent NDV strain LaSota has been used to generate live-attenuated genotype-matched NDV vaccines [15,16,19,24,25,26,27,28]. It is not known if this is the best avirulent FPCS to develop safe and effective genotype-matched NDV vaccines

Summary

Introduction

Newcastle disease virus (NDV) causes a severe disease in chickens worldwide. NDV is an enveloped virus belonging to family Paramyxoviridae. NDV has a negative-sense, nonsegmented RNA genome that contains six genes (3’-N-P-M-F-HN-L-5’) [1,2]. NDV contains two envelope glycoproteins, the hemagglutinin-neuraminidase (HN) protein and the fusion (F) protein. The HN protein is responsible for binding to cell surface receptor and the F protein is responsible for fusion between the viral envelope and the cell membrane [2,3]. The cleavage of F protein is the major determinant of NDV virulence [2,3,4,5]. The avirulent NDV strains have mono or dibasic residues at their F protein cleavage sites

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