A vaccine central in A(H5) influenza antigenic space confers broad immunity
Highly pathogenic avian influenza A(H5) viruses globally impact wild and domestic birds, and have caused severe infections in mammals, including humans, underscoring their pandemic potential<sup>1-5</sup>. The antigenic evolution of the A(H5) haemagglutinin (HA) poses challenges for pandemic preparedness and vaccine design<sup>6</sup>. Here the global antigenic evolution of the A(H5) HA was captured in a high-resolution antigenic map. The map was used to design immunogenic and antigenically central vaccine HA antigens, eliciting antibody responses that broadly cover the A(H5) antigenic space. In ferrets, a central antigen protected as well as homologous vaccines against heterologous infection with two antigenically distinct viruses. This work showcases the rational design of subtype-wide influenza A(H5) pre-pandemic vaccines and demonstrates the value of antigenic maps for the evaluation of vaccine-induced immune responses through antibody profiles.
Authors
- Judith M. A. van den Brand (ORCID: https://orcid.org/0000-0001-8420-5406)
- Pascal Lexmond
- Derek J. Smith (ORCID: https://orcid.org/0000-0002-2393-1890)
- Monique I. Spronken
- Theo M. Bestebroer
- Samuel Wilks (ORCID: https://orcid.org/0000-0002-7760-8474)
- Ron A. M. Fouchier (ORCID: https://orcid.org/0000-0001-8095-2869)
- David J. Pattinson (ORCID: https://orcid.org/0000-0003-0806-6832)
- Willemijn F. Rijnink (ORCID: https://orcid.org/0000-0003-3151-3725)
- Dennis de Meulder (ORCID: https://orcid.org/0000-0002-3631-4189)
- Adinda Kok (ORCID: https://orcid.org/0000-0003-3635-7952)
- Sarah L. James (ORCID: https://orcid.org/0000-0002-6969-1167)
- Sina Türeli
- Mathilde Richard (ORCID: https://orcid.org/0000-0003-0240-9312)
- Sander Herfst (ORCID: https://orcid.org/0000-0001-9866-8903)
- Miruna E. Rosu (ORCID: https://orcid.org/0000-0003-3469-7822)
- Mathis Funk (ORCID: https://orcid.org/0000-0001-7830-9989)
- David F. Burke (ORCID: https://orcid.org/0000-0001-8830-3951)
- Stefan van der Vliet
Institutions
- University of Wisconsin–Madison (US)
- The University of Melbourne (AU)
- King's College London (GB)
- Utrecht University (NL)
- University of Cambridge (GB)
- Erasmus MC (NL)
- Victoria University (AU)
- Erasmus University Rotterdam (NL)
Publication Details
- Journal
- Nature
- Published
- 2025-10-15
- DOI
- https://doi.org/10.1038/s41586-025-09626-3
- Citations
- 4
- Primary Topic
- Influenza Virus Research Studies
- Type
- article
- Field-Weighted Citation Impact
- 5.42