Field outbreak investigation and immunoinformatic analysis suggest potential immune evasion by Newcastle disease virus Sub-Genotype XIV.2 in Nigeria

Poultry production is one of the fastest-growing agricultural sub-sectors in Nigeria. However, it faces numerous challenges, mainly from frequent Newcastle disease (ND) outbreaks even in vaccinated flocks, causing huge economic losses. The recurring outbreaks raise concerns about the efficacy of ND vaccine and the need to understand the immunomodulatory mechanism of the ND virus (NDV). This study investigated a recent outbreak of NDV that resulted in 95% mortality in a vaccinated broiler parent stock in Nigeria by utilizing immunoinformatic tools to elucidate the possible immune evasion features of the disease-causing NDV. Genetic analysis of the complete fusion gene showed that the NDV isolate belong to sub-genotype XIV.2, a virulent strain prevalent in Nigeria. Predicted immunogenic peptides from the sub-genotype XIV.2 proteins revealed notable amino acid variations (R114Q, V118I, A220V) in both Major Histocompatibility Complex class I and II epitopes compared to common NDV vaccine and other prominent field strains. Modelling and structural validation of the BF2*2101 chicken allele showed 99% residues within the allowed regions in Ramachandran plot and - 6.61 Z-score, confirming its reliability. Immune simulation indicated that LaSota-Komorov prime-boost vaccine-simulation could not confer protection against sub-genotype XIV.2 virus simulated-challenge, despite eliciting humoral immune response. These results provide a valuable insight for developing ND vaccines that could effectively counter the immune cell interference of sub-genotype XIV.2, although further experimental validation is needed to characterize key biological interactions. A multifaceted approach encompassing improved biosecurity and the development of an effective sub-genotype XIV.2-matched vaccine is crucial to mitigate the persistent threat of ND in Nigeria.