A vaccine central in A(H5) influenza antigenic space confers broad immunity
- Adinda Kok
- Samuel H. Wilks
- Sina Tureli
- Sarah L. James
- Theo M. Bestebroer
- David F. Burke
- Mathis Funk
- Stefan van der Vliet
- Monique I. Spronken
- Willemijn F. Rijnink
- David J. Pattinson
- Dennis de Meulder
- Miruna E. Rosu
- Pascal Lexmond
- Judith M. A. van den Brand
- Sander Herfst
- Derek J. Smith
- Ron A. M. Fouchier
- Mathilde Richard
2025-10-15
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 1–5 . The antigenic evolution of the A(H5) haemagglutinin (HA) poses challenges for pandemic preparedness and vaccine design 6 . 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.