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

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.

Contributions of HA1 and HA2 Subunits of Highly Pathogenic Avian Influenza Virus in Induction of Neutralizing Antibodies and Protection in Chickens

“…Firstly, for NDV, a homologous virus was used in HI assay for the detection of antibodies against NDV, while for HPAIV, a heterologous LPAIV (H5N2), with about 90% amino acid identity with the HA protein of recombinant vaccine, was utilized to detect HI and neutralizing antibody titers against H5N1 HPAIV. Previous studies have shown that the antibody titers assayed against a heterologous H5 HPAIV were lower compared to the homologous H5 HPAIV virus (Swayne et al, 2015;Jang et al, 2018). Secondly, for HPAIV, antibodies induced against HA protein contribute to HI and VN assays.…”

High immune efficacy against different avian influenza H5N1 viruses by oral administration of a Saccharomyces cerevisiae-based vaccine in chickens

“…Due to serious limitations of manufacturing platform, currently available avian in uenza H5N1 vaccines are generally poorly immunogenic, and have safety concerns [6,21,22]. Furthermore, most of in uenza A (H5N1) vaccines require administration by intramuscular or subcutaneous injection, which have been shown to be insu cient for the generation of protective immunity at the mucosal surface [23].…”

“…Further, the egg-based manufacturing processes of these vaccines also have safety and production issues. A live-attenuated A (H5N1) vaccine had been generated by reverse genetics, but the risk of generating virus reassortment in the eld prohibits the use of this vaccine in most instances [6]. Thus, there is a clear need for new vaccine formulation and delivery strategies that can provide increased e cacy and safety.…”

A modified live bat influenza A virus-based vaccine prototype provides full protection against HPAIV H5N1

“…However, there are experiments which indicate that influenza live vaccines can "elicit higher levels of innate responses, mucosal IgA antibodies, and heterologous protection in 1-day-old chickens compared to IIV" 17 . Modified live influenza vaccines (MLIV) are able to induce a broad humoral (systemic and mucosal) and cellular immune response.…”