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Broad neuraminidase antibodies confer protection against seasonal and avian influenza viruses

Author

Listed:
  • Kexin Lv

    (Shenzhen Campus of Sun Yat-sen University)

  • Xiaoman Li

    (Tsinghua University)

  • Xingchen Zhu

    (Shenzhen Campus of Sun Yat-sen University)

  • Jian-Piao Cai

    (The University of Hong Kong)

  • Shuning Liu

    (Shenzhen Campus of Sun Yat-sen University)

  • Yuzhu Sun

    (Shenzhen Campus of Sun Yat-sen University)

  • Lin Liu

    (Shenzhen Campus of Sun Yat-sen University)

  • Xiaoyu Cai

    (Shenzhen Campus of Sun Yat-sen University)

  • Rui Cao

    (Shenzhen Campus of Sun Yat-sen University)

  • Mengxin Xu

    (Shenzhen Campus of Sun Yat-sen University)

  • Xinyu Yue

    (Shenzhen Campus of Sun Yat-sen University)

  • Yanmei Zhai

    (Shenzhen Campus of Sun Yat-sen University)

  • Wanyu Luo

    (Shenzhen Campus of Sun Yat-sen University)

  • Hongjie Lu

    (Shenzhen Campus of Sun Yat-sen University)

  • Ruiying Li

    (Shenzhen Campus of Sun Yat-sen University)

  • Haoting Mai

    (Shenzhen Campus of Sun Yat-sen University)

  • Lei Deng

    (Hunan University)

  • Feng Ye

    (The 74(th) Group Army Hospital)

  • Shifeng Chen

    (The 74(th) Group Army Hospital)

  • Mang Shi

    (Sun Yat-sen University)

  • Huanle Luo

    (Shenzhen Campus of Sun Yat-sen University)

  • Xinquan Wang

    (Tsinghua University)

  • Shuofeng Yuan

    (The University of Hong Kong)

  • Yuelong Shu

    (Shenzhen Campus of Sun Yat-sen University
    Chinese Academy of Medical Sciences & Peking Union Medical College)

  • Jiwan Ge

    (Chinese Academy of Medical Sciences & Peking Union Medical College)

  • Yao-Qing Chen

    (Shenzhen Campus of Sun Yat-sen University
    Shenzhen Key Laboratory of Pathogenic Microbes and Biosafety
    Ministry of Education)

Abstract

Neuraminidase (NA) is a critical target for universal influenza vaccines and therapeutic antibodies, yet its antigenic landscape remains incompletely understood. Here we identify two broadly cross-protective monoclonal antibodies, CAV-F6 and CAV-F34, from influenza-infected individuals. These antibodies inhibit NA enzymatic activity across multiple subtypes and confer protection against seasonal influenza in female mouse models. Importantly, the two antibodies also neutralize emerging avian strains, including recent bovine H5N1 and H7N9 strains, both with pandemic potential. Structural studies reveal that both antibodies target conserved regions of the NA active site via HCDR3, blocking sialic acid interaction. Furthermore, we observe distinct occupancy for the two antibodies on N2 tetramer, which is likely due to differences in binding affinity. Our findings provide molecular insights into NA-targeted immunity and offer a foundation for developing broadly protective influenza vaccines and therapeutics.

Suggested Citation

  • Kexin Lv & Xiaoman Li & Xingchen Zhu & Jian-Piao Cai & Shuning Liu & Yuzhu Sun & Lin Liu & Xiaoyu Cai & Rui Cao & Mengxin Xu & Xinyu Yue & Yanmei Zhai & Wanyu Luo & Hongjie Lu & Ruiying Li & Haoting M, 2025. "Broad neuraminidase antibodies confer protection against seasonal and avian influenza viruses," Nature Communications, Nature, vol. 16(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-62040-1
    DOI: 10.1038/s41467-025-62040-1
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    References listed on IDEAS

    as
    1. Chunyang Gu & Tadashi Maemura & Lizheng Guan & Amie J. Eisfeld & Asim Biswas & Maki Kiso & Ryuta Uraki & Mutsumi Ito & Sanja Trifkovic & Tong Wang & Lavanya Babujee & Robert Presler & Randall Dahn & Y, 2024. "A human isolate of bovine H5N1 is transmissible and lethal in animal models," Nature, Nature, vol. 636(8043), pages 711-718, December.
    2. Min Wang & Yuan Gao & Chenguang Shen & Wei Yang & Qi Peng & Jinlong Cheng & Han-Ming Shen & Yang Yang & George Fu Gao & Yi Shi, 2024. "A human monoclonal antibody targeting the monomeric N6 neuraminidase confers protection against avian H5N6 influenza virus infection," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    3. Atsuhiro Yasuhara & Seiya Yamayoshi & Maki Kiso & Yuko Sakai-Tagawa & Moe Okuda & Yoshihiro Kawaoka, 2022. "A broadly protective human monoclonal antibody targeting the sialidase activity of influenza A and B virus neuraminidases," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    4. Kenneth B Hoehn & Oliver G Pybus & Steven H Kleinstein, 2022. "Phylogenetic analysis of migration, differentiation, and class switching in B cells," PLOS Computational Biology, Public Library of Science, vol. 18(4), pages 1-24, April.
    5. Marina R. Good & Monica L. Fernández-Quintero & Wei Ji & Alesandra J. Rodriguez & Julianna Han & Andrew B. Ward & Jenna J. Guthmiller, 2024. "A single mutation in dairy cow-associated H5N1 viruses increases receptor binding breadth," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
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