Nature communications · 2026
Potent efficacy of an NA-targeting antibody against a broad spectrum of H5N1 influenza viruses.
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Moriyama Saya, di Iulio Julia, Zatta Fabrizia, Hauser Kevin, Asanuma Hideki, Muñoz Hector E, Errico John M, Adachi Yu, Dang Ha V, Czudnochowski Nadine, Sasaki Eita, Chen Alex, Chen Yi-Pei, Kotaki Ryutaro, Peter Alessia, Vetti Eneida, Onodera Taishi, Cyrus Maher M, Rosen Laura E, Shirakura Masayuki, Snell Gyorgy, Hasegawa Hideki, Takahashi Yoshimasa, Corti Davide, Pizzuto Matteo Samuele
Аннотация
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.