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Identification of a broad-inhibition influenza neuraminidase antibody from pre-existing memory B cells

文献类型： 外文期刊

作者： Wang, Xin 1 ; Kong, Huihui 5 ; Chu, Bingxin 4 ; Yang, Qian 1 ; Lin, Chaohui 1 ; Liu, Rui 3 ; Chen, Changxu 3 ; Gao, Yang 9 ; Wang, Guojun 9 ; Wang, Dayan 10 ; Qin, Chen 5 ; Ye, Xiaohua 1 ; Yu, Lifei 8 ; Xu, Xiangfei 8 ; Jin, Jie 8 ; Sun, Ren 1 ; Chen, Hualan 5 ; Wu, Xudong 6 ; Zhang, Zeli 1 ;

作者机构： 1.Westlake Univ, Sch Med, Zhejiang Key Lab Multiom Infect & Immun, Ctr Infect Dis Res, Hangzhou, Zhejiang, Peoples R China

2.Westlake Univ, Res Ctr Ind Future, Hangzhou, Zhejiang, Peoples R China

3.Westlake Univ, Sch Life Sci, Hangzhou, Zhejiang, Peoples R China

4.Westlake Univ, Sch Life Sci, Key Lab Struct Biol Zhejiang Prov, Hangzhou, Zhejiang, Peoples R China

5.Chinese Acad Agr Sci, Harbin Vet Res Inst, State Key Lab Anim Dis Control, Harbin, Peoples R China

6.Westlake Lab Life Sci & Biomed, Hangzhou, Zhejiang, Peoples R China

7.Westlake Inst Adv Study, Inst Biol, Hangzhou, Zhejiang, Peoples R China

8.Westlake Univ, Affiliated Hangzhou Peoples Hosp 1, Sch Med, Hangzhou, Zhejiang, Peoples R China

9.Inner Mongolia Univ, State Key Lab Reprod Regulat & Breeding Grassland, Coll Life Sci, Hohhot, Peoples R China

10.Chinese Ctr Dis Control & Prevent, Natl Inst Viral Dis Control & Prevent, Beijing, Peoples R China

11.WHO Collaborating Ctr Reference & Res Influenza, Beijing, Peoples R China

期刊名称：CELL HOST & MICROBE （ 影响因子：18.7； 五年影响因子：20.5 ）

ISSN： 1931-3128

年卷期： 2025 年 33 卷 1 期

页码：

收录情况： SCI

摘要： Identifying broadly reactive B precursor cells and conserved epitopes is crucial for developing a universal flu vaccine. In this study, using influenza neuraminidase (NA) mutant probes, we find that human pre-existing NA-specific memory B cells (MBCs) account for '0.25% of total MBCs, which are heterogeneous and dominated by class-unswitched MBCs. In addition, we identify three NA broad-inhibition monoclonal antibodies (mAbs) (BImAbs) that block the activity of NA derived from different influenza strains, including the recent cow H5N1. The cryoelectron microscopy (cryo-EM) structure shows that the BImAb targets the conserved NA enzymatic pocket and a separate epitope in the neighboring NA monomer. Furthermore, the NA BImAbs protect mice from the lethal challenge of the human pandemic H1N1 and H5N1. Our work demonstrates that the NA broad-inhibition precursor MBCs exist in healthy adults and could be targeted by the NA-based universal flu vaccine.

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