Efficacy and synergy of live-attenuated and inactivated influenza vaccines in young chickens

PLoS One. 2018 Apr 6;13(4):e0195285. doi: 10.1371/journal.pone.0195285. eCollection 2018.


Outbreaks of novel highly pathogenic avian influenza viruses have been reported in poultry species in the United States since 2014. These outbreaks have proven the limitations of biosecurity control programs, and new tools are needed to reinforce the current avian influenza control arsenal. Some enzootic countries have implemented inactivated influenza vaccine (IIV) in their control programs, but there are serious concerns that a long-term use of IIV without eradication may result in the selection of novel antigenically divergent strains. A broadly protective vaccine is needed, such as live-attenuated influenza vaccine (LAIV). We showed in our previous studies that pc4-LAIV (a variant that encodes a C-terminally truncated NS1 protein) can provide significant protection against heterologous challenge virus in chickens vaccinated at 2-4 weeks of age through upregulation of innate and adaptive immune responses. The current study was conducted to compare the performances of pc4-LAIV and IIV in young chickens vaccinated at 1 day of age. A single dose of pc4-LAIV was able to induce stronger innate and mucosal IgA responses and protect young immunologically immature chickens better than a single dose of IIV. Most importantly, when 1-day-old chickens were intranasally primed with pc4-LAIV and subcutaneously boosted with IIV three weeks later, they showed a rapid, robust, and highly cross-reactive serum antibody response and a high level of mucosal IgA antibody response. This vaccination regimen warrants further optimization to increase its range of protection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Antibodies, Viral / biosynthesis
  • Antibodies, Viral / blood
  • Antibodies, Viral / genetics
  • Antigens, Viral / genetics
  • Chickens / immunology*
  • Cross Reactions
  • Immunity, Innate / genetics
  • Immunity, Mucosal / genetics
  • Immunization, Secondary / methods
  • Immunization, Secondary / veterinary
  • Influenza A virus / genetics
  • Influenza A virus / immunology
  • Influenza Vaccines / administration & dosage*
  • Influenza Vaccines / genetics
  • Influenza Vaccines / immunology
  • Influenza in Birds / immunology*
  • Influenza in Birds / prevention & control*
  • Poultry Diseases / immunology*
  • Poultry Diseases / prevention & control*
  • Vaccination / methods
  • Vaccination / veterinary
  • Vaccines, Attenuated / administration & dosage
  • Vaccines, Attenuated / genetics
  • Vaccines, Attenuated / immunology
  • Vaccines, Inactivated / administration & dosage
  • Vaccines, Inactivated / genetics
  • Vaccines, Inactivated / immunology


  • Antibodies, Viral
  • Antigens, Viral
  • Influenza Vaccines
  • Vaccines, Attenuated
  • Vaccines, Inactivated

Grants and funding

This work was supported by Agriculture and Food Research Initiative Competitive Grant no. 2013-67015-20476 from the USDA National Institute of Food and Agriculture; Doctoral SEEDS Grant no. OHOA1006 from the Ohio Agricultural Research and Development Center.