Genotype-matched Newcastle disease virus vaccine confers improved protection against genotype XII challenge: The importance of cytoplasmic tails in viral replication and vaccine design

PLoS One. 2019 Nov 14;14(11):e0209539. doi: 10.1371/journal.pone.0209539. eCollection 2019.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Line
  • Chickens
  • Genotype
  • Newcastle Disease / immunology*
  • Newcastle Disease / prevention & control*
  • Newcastle Disease / virology
  • Newcastle disease virus / classification
  • Newcastle disease virus / genetics*
  • Newcastle disease virus / immunology*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology
  • Sequence Homology, Amino Acid
  • Vaccines, Synthetic / genetics
  • Vaccines, Synthetic / immunology
  • Viral Proteins / genetics
  • Viral Proteins / immunology
  • Viral Vaccines / genetics*
  • Viral Vaccines / immunology*
  • Virulence / genetics
  • Virulence / immunology
  • Virus Replication / genetics
  • Virus Replication / immunology
  • Virus Shedding / genetics
  • Virus Shedding / immunology

Substances

  • Recombinant Fusion Proteins
  • Vaccines, Synthetic
  • Viral Proteins
  • Viral Vaccines

Grants and funding

This study was partially funded by the Peruvian Science and Technology Program (FINCyT) contract nº ITAI-2-P-050-009-15. There was no additional external funding received for this study.