Digitally Immune-Optimised Next-Generation Influenza H5Nx Vaccination Provides Protection with Broad Cross-Clade Neutralisation Against Global Threats

A panzootic of H5Nx avian influenza viruses has severely affected poultry and wild bird populations, resulting in multiple mammalian spillovers, including mild to fatal human infections caused by antigenically distinct and diverse virus clades. The unpredictable nature of spillover events of antigenically drifted H5Nx viruses hinders our ability to effectively respond to the heightened risk of human-to-human transmission. Stockpiled strain-specific H5 whole virus-based vaccines provide limited breadth and reduced efficacy. To address this problem, we computationally designed vaccine antigens that induce broad protective immune responses. Ferrets immunised with the DVX-panH5Nx mRNA vaccine candidate generated potent broad immune responses across a wide spectrum of A/H5 clades. Furthermore, ferrets immunised with DVX-pan-H5Nx demonstrated superior protection and immune breadth when compared to an industry standard inactivated vaccine derived from candidate virus vaccine A/Astrakhan/3212/2020 (H5N8), against a lethal heterologous challenge.