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.
Highlights
Avian influenza viruses (AIVs) pose a constant threat to the poultry industry with avian influenza (AI) outbreaks resulting in significant economic losses [1,2,3,4,5]
This was in clear contrast with pc2-live attenuated influenza vaccine (LAIV) vaccination where none of the birds were HI positive or reverse genetically created wildtype (rgWT) infection where only 2 birds had detectable antibodies at this time point
To rule out the possibility that the rapid and high ratio of seroconversion in the pc4-LAIVvaccination group was due to high replication efficiency of the vaccine virus, viral titers were determined from tracheal swabs
Summary
Avian influenza viruses (AIVs) pose a constant threat to the poultry industry with avian influenza (AI) outbreaks resulting in significant economic losses [1,2,3,4,5]. During the 2015 highly pathogenic avian influenza (HPAI) outbreak in the Midwest, more than 40 million birds were killed and 10% of the US egg supply was affected [6]. In addition to their devastating impact on the poultry industry, occasional direct transmission of AIVs from poultry to humans has resulted in serious outbreaks in the past that produced fatal outcomes [7, 8]. The recent avian H5N1, H7N7, and H7N9 human outbreaks in China and Europe have come with severe respiratory illness resulting in severe respiratory symptoms and death in some cases [8,9,10].
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