Abstract
Although typical Newcastle disease virus (NDV) vaccines can prevent mortality, they are not effective in preventing viral shedding. To overcome this, genotype-matched vaccines have been proposed. To date, this approach has never been tested against genotype XII strains. In this study, we generated and assessed the protection against genotype XII challenge of two chimeric NDV vaccine strains (rLS1-XII-1 and rLS1-XII-2). The rLS1-XII-1 virus has the complete fusion protein (F) and the hemagglutinin-neuraminidase (HN) open reading frames replaced with those from genotype XII strain NDV/peacock/Peru/2011 (PP2011) in a recombinant LaSota (rLS1) backbone. In rLS1-XII-2 virus, cytoplasmic tails of F and HN proteins were restored to those of rLS1. In vitro evaluation showed that rLS1-XII-2 and the parental rLS1 strains replicate at higher efficiencies than rLS1-XII-1. In the first vaccine/challenge experiment, SPF chickens vaccinated with rLS1-XII-1 virus showed only 71.3% protection, whereas, rLS1 and rLS1-XII-2 vaccinated chickens were fully protected. In a second experiment, both rLS1-XII-2 and the commercial vaccine strain LaSota induced 100% protection. However, rLS1-XII-2 virus significantly reduced viral shedding, both in the number of shedding birds and in quantity of shed virus. In conclusion, we have developed a vaccine candidate capable of fully protecting chickens against genotype XII challenges. Furthermore, we have shown the importance of cytoplasmic tails in virus replication and vaccine competence.
Highlights
Newcastle disease virus (NDV) is a widely distributed virus that affects poultry and other avian species [1]
DF-1 cells were infected with either rLS1, rLS1-XII-1, rLS1-XII-2 viruses or mock-infected at a multiplicity of infection (MOI) of 0.01 for 1 hour, washed with Dulbecco’s phosphate-buffered saline (DPBS) and covered with Dulbecco’s modified Eagle medium (DMEM) semisolid media (0.75% methylcellulose + 2% fetal bovine serum (FBS) + 5% allantoic fluids (AFs))
Presence of homologous cytoplasmic tails in F and HN proteins results in a higher viral replication compared to heterologous cytoplasmic tails
Summary
Newcastle disease virus (NDV) is a widely distributed virus that affects poultry and other avian species [1]. NDV genome encodes six structural genes: Nucleoprotein (N), phosphoprotein (P), matrix (M), fusion (F), hemagglutinin-neuraminidase (HN) and large polymerase (L) [4] From these proteins, M, HN and F form the envelope. Many authors have suggested that antigenic matches of F and HN proteins between vaccine and challenge strains are capable to improve live-attenuated vaccine protection by significantly reducing viral sheading [21,22]. To assess whether genotype XII matched vaccine can improve protection against a homologous challenge, we generated by reverse genetics two recombinant NDV (rNDV) strains containing both F and HN proteins from the genotype XIIa strain NDV/peacock/Peru/2011 (PP2011) [14] in the rLS1 backbone [28]. RLS1-XII-2 virus and the commercial vaccine LaSota strain were compared for their capacity to induce protection, specific antibodies and reduce viral shedding
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