Abstract
Newcastle disease (ND), caused by Newcastle disease virus (NDV), the virulent form of avian orthoavulavirus type 1 (AOAV-1), is regarded as one of the most important avian diseases worldwide. Vaccination against ND has historically been limited in its ability to control the spread of the virus, but has continued to reduce the burden of clinical disease.
To improve our understanding of factors that contribute to vaccine efficacy, 22 AOAV-1 isolates were sequenced that represent the full range of genetic and antigenic diversity. A comprehensive analysis was undertaken based on fusion (F) and hemagglutinin-neuraminindase (HN) protein sequences identifying thirteen novel amino acid substitutions. Based on these mutations, 3D predicted structural protein models were generated to assess the structural properties of antigenic sites, providing evidence that substitutions have a potential to impact on epitope recognition and subsequent vaccine failure. In total, 16 isolates were selected for further in-depth assessment through the application of binding assays to understand antigenic relationships highlighting that cross-hemagglutinin inhibition data which forms the basis for AOAV serotyping offers very little discrimination. However, cross-virus neutralisation assays show a number of outliers providing growing evidence that AOAV-1 is antigenically evolving. Utilising this data, antigenic cartography was performed for the first time to visualise and quantify the antigenic relationships of AOAV-1 demonstrating that antigenic cartography is applicable to AOAV-1 and can be accurately represented in 3D maps. Whilst they generally support the outputs from traditional statistical analysis, they reveal that AOAV-1 does not form a single cluster demonstrating that AOAV-1 is evolving slowly.
Overall, the results of this study have shown that although AOAV-1 is considered a single serotype, measurable differences have been observed taking us a step closer to understanding the antigenic relations of AOAV-1 and thereby helping the control of ND and supporting the world’s poultry production and food security.