Association between Interferon Response and Protective Efficacy of NS1-Truncated Mutants as Influenza Vaccine Candidates in Chickens

PLoS One. 2016 Jun 3;11(6):e0156603. doi: 10.1371/journal.pone.0156603. eCollection 2016.

Abstract

Influenza virus mutants that encode C-terminally truncated NS1 proteins (NS1-truncated mutants) are attractive candidates for avian live attenuated influenza vaccine (LAIV) development because they are both attenuated and immunogenic in chickens. We previously showed that a high protective efficacy of NS1-truncated LAIV in chickens corresponds with induction of high levels of type I interferon (IFN) responses in chicken embryonic fibroblast cells. In this study, we investigated the relationship between induction of IFN and IFN-stimulated gene responses in vivo and the immunogenicity and protective efficacy of NS1-truncated LAIV. Our data demonstrates that accelerated antibody induction and protective efficacy of NS1-truncated LAIV correlates well with upregulation of IFN-stimulated genes. Further, through oral administration of recombinant chicken IFN alpha in drinking water, we provide direct evidence that type I IFN can promote rapid induction of adaptive immune responses and protective efficacy of influenza vaccine in chickens.

MeSH terms

  • Adaptive Immunity
  • Administration, Oral
  • Animals
  • Antibodies, Viral / blood
  • Chickens
  • Influenza Vaccines / immunology*
  • Influenza in Birds / prevention & control*
  • Influenza in Birds / virology
  • Interferons / immunology*
  • Interferons / pharmacology
  • Mutation
  • Recombinant Proteins / immunology
  • Vaccines, Attenuated / immunology
  • Viral Nonstructural Proteins / genetics
  • Viral Nonstructural Proteins / immunology*

Substances

  • Antibodies, Viral
  • INS1 protein, influenza virus
  • Influenza Vaccines
  • Recombinant Proteins
  • Vaccines, Attenuated
  • Viral Nonstructural Proteins
  • Interferons

Grants and funding

This study was supported by the SEEDS fund (2012009) and other funds from the Ohio Agricultural Research and Development Center, The Ohio State University.