ABSTRACT
The increasing global spread of the highly pathogenic avian influenza (HPAI) A/H5 viruses poses a serious public health threat. Circulating clade 2.3.4.4b viruses have demonstrated rapid transcontinental dissemination, extensive reassortment, epizootic spread and potential sustained mammal-to-mammal transmission, signifying a heightened risk of becoming a human pathogen of high consequence. A broadly protective, future-proof vaccine against multiple clades of H5 influenza is urgently needed for pandemic preparedness. Here, we combine two novel vaccine technologies to generate a Digitally Immune Optimised and Selected H5 antigen (DIOSvax-H5inter) displayed multivalently on the mi3 nanocage using the SpyTag003/SpyCatcher003 conjugation system. Mice immunised with DIOSvax-H5inter Homotypic Nanocages at low doses demonstrate potent, cross-clade neutralising antibody and T cell responses against diverse H5 strains. DIOSvax-H5inter Homotypic Nanocages provide a scalable vaccine candidate with the potential for pan-H5 protection against drifted or newly emergent H5 strains. This World Health Organization preferred product characteristic is essential for prospective strategic stockpiling in the pre-pandemic phase.
Competing Interest Statement
J.L.H., G.W.C., S.V. and S.D.W.F. developed, tested and validated the H5 antigen DIOSvax-H5inter by gene delivery and are inventors of patent applications on computational vaccine development methods (US20220040284A1) and influenza vaccines (US20230149530A1). J.L.H. and S.D.W.F. are co-founders and shareholders of DIOSynVax Ltd. M.R.H. is a co-founder and shareholder of SpyBiotech. M.R.H. is an inventor on a patent on spontaneous amide bond formation (EP2534484) and a patent on SpyTag003:SpyCatcher003 (UK Intellectual Property Office 1706430.4). S.D.W.F. is an employee of Microsoft. All other authors have no competing interests to declare.
