Potent efficacy of an NA-targeting antibody against a broad spectrum of H5N1 influenza viruses

For nearly 30 years, Goose/Guangdong-derived highly pathogenic avian influenza H5N1 viruses have posed significant risks to economic stability, food security, and public health. Virus evolution has resulted in various clades, including the panzootic subclade 2.3.4.4b, recognized for its pandemic potential. Here we present the potent in vitro activity of FNI9, a pan-influenza NA-inhibiting monoclonal antibody, against a range of pseudoparticles with NA spanning decades of H5N1 virus evolution. FNI9 also shows strong prophylactic protection in female mice against lethal challenges with H5N1 from clade 1 and 2.3.4.4b. Cryo-EM and molecular dynamics analysis reveal that FNI9 binds to 7 highly conserved H5N1 NA residues (R118, E119, D151, E228, E278, R293, and R368). In silico evolutionary escape profiling and machine learning predict low escapability, high fitness costs, and minimal spread likelihood for viral mutations that evade FNI9 binding. These findings support FNI9 broad protection and underscore the NA role in future influenza vaccine design.

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Publication Details

Journal
Nature Communications
Published
2026-03-02
DOI
https://doi.org/10.1038/s41467-026-70036-8
Primary Topic
Influenza Virus Research Studies
Type
article
Field-Weighted Citation Impact
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article

Potent efficacy of an NA-targeting antibody against a broad spectrum of H5N1 influenza viruses

Fabrizia Zatta, Alessia Peter, Matteo Samuele Pizzuto, Laura E. Rosen et al.
Nature Communications
Influenza Virus Research Studies
article

Potent efficacy of an NA-targeting antibody against a broad spectrum of H5N1 influenza viruses

Fabrizia Zatta, Alessia Peter, Matteo Samuele Pizzuto, Laura E. Rosen, Yoshimasa Takahashi, Kevin Hauser, Eneida Vetti, Hector E. Muñoz, Saya Moriyama, Yi-Pei Chen, John M. Errico, Julia di Iulio, Ryutaro Kotaki, Nadine Czudnochowski, Masayuki Shirakura, Alex Chen, Yu Adachi, Ha V. Dang, Taishi Onodera, Hideki Hasegawa, Hideki Asanuma, Davide Corti, M. Cyrus Maher, Gyorgy Snell, Eita Sasaki
article en

Abstract

For nearly 30 years, Goose/Guangdong-derived highly pathogenic avian influenza H5N1 viruses have posed significant risks to economic stability, food security, and public health. Virus evolution has resulted in various clades, including the panzootic subclade 2.3.4.4b, recognized for its pandemic potential. Here we present the potent in vitro activity of FNI9, a pan-influenza NA-inhibiting monoclonal antibody, against a range of pseudoparticles with NA spanning decades of H5N1 virus evolution. FNI9 also shows strong prophylactic protection in female mice against lethal challenges with H5N1 from clade 1 and 2.3.4.4b. Cryo-EM and molecular dynamics analysis reveal that FNI9 binds to 7 highly conserved H5N1 NA residues (R118, E119, D151, E228, E278, R293, and R368). In silico evolutionary escape profiling and machine learning predict low escapability, high fitness costs, and minimal spread likelihood for viral mutations that evade FNI9 binding. These findings support FNI9 broad protection and underscore the NA role in future influenza vaccine design.

Nature Communications
Hokkaido University (JP), Hokkaido Pharmaceutical University (JP), National Institute of Infectious Diseases (JP), Vir Biotechnology (Switzerland) (CH), VIR Biotechnology (United States) (US)
Good health and well-being
Openalex Percentile: Top 38%
Influenza Virus Research Studies
DOIOpen Access PDFOpenAlex
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