Enhancing protective efficacy of avian influenza vaccines through targeted delivery of protective antigens to chicken immune cells

Avian influenza viruses (AIVs) are highly contagious viruses that are widespread in birds. Wild aquatic birds (e.g., waterfowls, gulls, and shorebirds) are their natural hosts. However, they can be easily transmitted between different bird species and infect gallinaceous poultry including chickens, quails, and turkeys, resulting in severe economic losses. AIVs also pose a significant zoonotic and pandemic threats. Most of the commercially available avian influenza vaccines for poultry are inactivated whole virus vaccines that have several drawbacks including sub-optimal immunogenicity, need for multiple dose administration and interference from maternally derived antibodies (MDAs). Here, the immunogenicity and protective efficacy of recombinant subunit poultry AIV vaccine were enhanced by selective delivery of antigens to the professional antigen presenting cells (APCs) like dendritic cells and macrophages. This led us to the development of targeted antigen delivery vaccines whereby the haemagglutinin (HA) protein of H9N2 AIV was fused to single chain fragment variable antibodies (scFv) specific to chicken Dec205, CD11c and CD83 receptors. Out of the three targeted antigens tested, CD83 targeting induced higher serum haemagglutinin inhibition and virus neutralising antibodies compared to the untargeted H9HA and inactivated H9N2 vaccine. Furthermore, chickens vaccinated with CD83 targeted H9HA showed a reduced virus shedding post challenge compared to the untargeted H9HA, as well as a reduced interference from H9HA-specific MDAs. Overall, CD83 targeted H9HA was able to generate antibodies that were cross-reactive against different heterologous H9N2 viruses. Following on, the recombinant Herpesvirus of Turkey (rHVT) was also assessed for its use as a viral vector for in vivo expression of secreted and native membrane bound forms of H9HA antigen. The antibody titres generated by rHVT expressing native membrane bound H9HA was higher than any of the secreted forms. Overall, these results will assist in developing the next generation vaccines for preventing animal and human infectious diseases