Repurposing RIPK3 inhibitor GSK840 as an enhancer of the safety and immunogenicity of lentogenic Newcastle disease virus La Sota used for in ovo and spray vaccination.

GSK840 improves lentogenic NDV La Sota vaccine safety and immunogenicity in poultry via myosin modulation.

This study addresses critical safety limitations of lentogenic Newcastle disease virus (NDV) La Sota vaccine used in poultry. Live ND vaccines cause adverse reactions during spray vaccination of day-old chicks and reduce hatchability when administered in ovo. The researchers identified upregulation of inflammatory and cell death-related genes, particularly RIPK2, in chicken lungs following in ovo La Sota vaccination. Leveraging the structural homology between chicken RIPK2 and mammalian RIPK3, they investigated GSK840, a RIPK3 inhibitor targeting the DFG motif. Co-administration of GSK840 with La Sota significantly improved hatchability, post-hatch survival, and antibody responses. GSK840 pre-treatment prevented tracheal pathology and enhanced immunogenicity in spray-vaccinated chicks. Notably, pull-down assays with biotin-conjugated GSK840 and mass spectrometry identified multiple myosins (~200 kDa) as primary targets in chicken trachea, rather than RIPK2. These findings suggest GSK840 enhances both safety and immunogenicity of ND vaccination through myosin-related mechanisms, offering practical implications for optimizing live ND vaccine protocols in commercial poultry operations.

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