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bioRxiv · 10.1101/2024.11.14.623359

Digitally immune optimised haemagglutinin with nanocage plug-and-display elicits broadly neutralising pan-H5 influenza subtype vaccine responses

Huang, C. Q.·Hills, R. A.·Carnell, G. W.·Vishwanath, S.·Aguinam, E. T.·Chan, A. C. Y.·Palmer, P.·O'Reilly, L.·Tonks, P.·Temperton, N.·Frost, S. D. W.·Tiley, L. S.·Howarth, M. R.·Heeney, J. L.
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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.

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Huang, C. Q., Hills, R. A., Carnell, G. W., Vishwanath, S., Aguinam, E. T., Chan, A. C. Y., Palmer, P., O'Reilly, L., Tonks, P., Temperton, N., Frost, S. D. W., Tiley, L. S., Howarth, M. R., Heeney, J. L.. 2024-11-15. Digitally immune optimised haemagglutinin with nanocage plug-and-display elicits broadly neutralising pan-H5 influenza subtype vaccine responses. https://doi.org/10.1101/2024.11.14.623359

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