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

doi:10.1038/s41586-025-09626-3

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^*

^*Corresponding author for this work

Virology

Utrecht University
University of Cambridge

Research output: Contribution to journal › Article › Academic › peer-review

4 Citations (Scopus)

11 Downloads (Pure)

Abstract

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, 2, 3, 4–5}. The antigenic evolution of the A(H5) haemagglutinin (HA) poses challenges for pandemic preparedness and vaccine design⁶. 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.

Original language	English
Pages (from-to)	1005-1013
Number of pages	9
Journal	Nature
Volume	647
Issue number	8091
DOIs	https://doi.org/10.1038/s41586-025-09626-3
Publication status	Published - 27 Nov 2025

Bibliographical note

Publisher Copyright:
© The Author(s) 2025.

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This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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A vaccine central in A(H5) influenza antigenic space confers broad immunityFinal published version, 21.2 MBLicence: CC BY

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Kok, A., Wilks, S. H., Tureli, S., James, S. L., Bestebroer, T. M., Burke, D. F., Funk, M., van der Vliet, S., Spronken, M. I., Rijnink, W. F., Pattinson, D. J., de Meulder, D., Rosu, M. E., Lexmond, P., van den Brand, J. M. A., Herfst, S., Smith, D. J., Fouchier, R. A. M., & Richard, M. (2025). A vaccine central in A(H5) influenza antigenic space confers broad immunity. Nature, 647(8091), 1005-1013. https://doi.org/10.1038/s41586-025-09626-3

@article{36f4ec647df7433b9780b4322cb7df06,

title = "A vaccine central in A(H5) influenza antigenic space confers broad immunity",

abstract = "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 potential1, 2, 3, 4–5. The antigenic evolution of the A(H5) haemagglutinin (HA) poses challenges for pandemic preparedness and vaccine design6. 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.",

author = "Adinda Kok and Wilks, \{Samuel H.\} and Sina Tureli and James, \{Sarah L.\} and Bestebroer, \{Theo M.\} and Burke, \{David F.\} and Mathis Funk and \{van der Vliet\}, Stefan and Spronken, \{Monique I.\} and Rijnink, \{Willemijn F.\} and Pattinson, \{David J.\} and \{de Meulder\}, Dennis and Rosu, \{Miruna E.\} and Pascal Lexmond and \{van den Brand\}, \{Judith M.A.\} and Sander Herfst and Smith, \{Derek J.\} and Fouchier, \{Ron A.M.\} and Mathilde Richard",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2025.",

year = "2025",

month = nov,

day = "27",

doi = "10.1038/s41586-025-09626-3",

language = "English",

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Kok, A, Wilks, SH, Tureli, S, James, SL, Bestebroer, TM, Burke, DF, Funk, M, van der Vliet, S, Spronken, MI, Rijnink, WF, Pattinson, DJ, de Meulder, D, Rosu, ME, Lexmond, P , van den Brand, JMA , Herfst, S, Smith, DJ, Fouchier, RAM & Richard, M 2025, 'A vaccine central in A(H5) influenza antigenic space confers broad immunity', Nature, vol. 647, no. 8091, pp. 1005-1013. https://doi.org/10.1038/s41586-025-09626-3

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AU - Kok, Adinda

AU - Wilks, Samuel H.

AU - Tureli, Sina

AU - James, Sarah L.

AU - Bestebroer, Theo M.

AU - Burke, David F.

AU - Funk, Mathis

AU - van der Vliet, Stefan

AU - Spronken, Monique I.

AU - Rijnink, Willemijn F.

AU - Pattinson, David J.

AU - de Meulder, Dennis

AU - Rosu, Miruna E.

AU - Lexmond, Pascal

AU - van den Brand, Judith M.A.

AU - Herfst, Sander

AU - Smith, Derek J.

AU - Fouchier, Ron A.M.

AU - Richard, Mathilde

PY - 2025/11/27

Y1 - 2025/11/27

N2 - 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 potential1, 2, 3, 4–5. The antigenic evolution of the A(H5) haemagglutinin (HA) poses challenges for pandemic preparedness and vaccine design6. 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.

AB - 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 potential1, 2, 3, 4–5. The antigenic evolution of the A(H5) haemagglutinin (HA) poses challenges for pandemic preparedness and vaccine design6. 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.

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EP - 1013

JO - Nature

JF - Nature

IS - 8091

ER -

A vaccine central in A(H5) influenza antigenic space confers broad immunity

Abstract

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