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<p>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月2日

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

摘要

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.