Abstract

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.

Highlights

  • Avian influenza (AI) is a major zoonotic viral disease that causes significant adverse impacts on poultry production, the global trade, and public health [1,2,3,4]

  • We previously demonstrated that upregulation of IFN-related genes by influenza vaccine correlates well with rapid induction of adaptive immune responses and enhancement of protective efficacy in 4-week-old chickens [32]

  • The ability of live-attenuated influenza vaccine (LAIV) and inactivated influenza vaccine (IIV) to stimulate innate immune responses in 1-day-old chickens was assessed by quantification of Messenger RNA (mRNA) transcription level of type I/II IFNs and interferon stimulated gene (ISG)

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Summary

Introduction

Avian influenza (AI) is a major zoonotic viral disease that causes significant adverse impacts on poultry production, the global trade, and public health [1,2,3,4]. The current biosecurity systems have repeatedly failed to protect poultry farms from introduction of novel strains that continue to cause major outbreaks [11, 12] To overcome this challenge, some countries have incorporated vaccination with inactivated influenza vaccine (IIV) in their control programs [10, 13]. The United States has been using ‘stamping out’ as the primary control strategy, but the occurrence of recent highly pathogenic avian influenza (HPAI) outbreaks [13, 14] further proves the limitations of stamping out in combination with biosecurity control For this reason, vaccination is being more seriously considered to be added to the country’s AI control arsenal. In addition to having a narrow range of protection, there are serious concerns that a long-term use of IIV without eradication of heterologous (mismatched) strains may result in the selection of antigenically divergent strains [17]

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