Computationally designed haemagglutinin with nanocage plug-and-display elicits pan-H5 influenza vaccine responses
The increasing spread of highly pathogenic avian influenza (HPAI) A/H5 viruses poses a pandemic 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-H5<sub>inter</sub>) displayed multivalently on the mi3 nanocage using the SpyTag003/SpyCatcher003 conjugation system. Mice immunized with DIOSvax-H5<sub>inter</sub> Homotypic Nanocages at low doses demonstrate potent, cross-clade neutralizing antibody and T cell responses against diverse H5 strains. DIOSvax-H5<sub>inter</sub> 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 characteristic is essential for prospective strategic stockpiling in the pre-pandemic phase.
Authors
- George Carnell (ORCID: https://orcid.org/0000-0001-8875-0989)
- Ernest T. Aguinam (ORCID: https://orcid.org/0000-0003-2099-982X)
- Lorraine A. O’Reilly (ORCID: https://orcid.org/0000-0001-7134-6496)
- Mark Howarth (ORCID: https://orcid.org/0000-0001-8870-7147)
- Phil Palmer (ORCID: https://orcid.org/0000-0002-9576-7540)
- Jonathan Luke Heeney (ORCID: https://orcid.org/0000-0003-2702-1621)
- Sneha Vishwanath (ORCID: https://orcid.org/0000-0001-9960-547X)
- Rory A. Hills (ORCID: https://orcid.org/0000-0002-5698-9538)
- Chloe Qingzhou Huang (ORCID: https://orcid.org/0009-0009-1503-1030)
- Simon D. W. Frost (ORCID: https://orcid.org/0000-0002-5207-9879)
- Nigel James Temperton (ORCID: https://orcid.org/0000-0002-7978-3815)
- Laurence Tiley (ORCID: https://orcid.org/0000-0002-3799-3611)
- Paul Tonks
- Andrew C.Y. Chan (ORCID: https://orcid.org/0009-0003-0955-6697)
Institutions
- Microsoft (United States) (US)
- University of Nottingham (GB)
- Loughborough University (GB)
- Medway School of Pharmacy (GB)
- University of Cambridge (GB)
- University of Oxford (GB)
- London School of Hygiene & Tropical Medicine (GB)
- Herts and Essex Hospital (GB)
Publication Details
- Journal
- Emerging Microbes & Infections
- Published
- 2025-06-06
- DOI
- https://doi.org/10.1080/22221751.2025.2511132
- Citations
- 3
- Primary Topic
- Influenza Virus Research Studies
- Type
- article
- Field-Weighted Citation Impact
- 4.06
Funders
- Bill and Melinda Gates Foundation
- Bill and Melinda Gates Institute for Population and Reproductive Health
- Flu Lab
- Rhodes Scholarships
- University of Cambridge
- Croucher Foundation
- Cambridge Trust
- Innovate UK