Broad neuraminidase antibodies confer protection against seasonal and avian influenza viruses

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 Mai, Lei Deng, Feng Ye, Shifeng Chen, Mang Shi, Huanle Luo, Xinquan Wang, Shuofeng Yuan (), Yuelong Shu (), Jiwan Ge () and Yao-Qing Chen ()
Additional contact information
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
Jiwan Ge: Chinese Academy of Medical Sciences & Peking Union Medical College
Yao-Qing Chen: Shenzhen Campus of Sun Yat-sen University

Nature Communications, 2025, vol. 16, issue 1, 1-14

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-62040-1

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