Identification of a broad-inhibition influenza neuraminidase antibody from pre-existing memory B cells
文献类型: 外文期刊
作者: Xin Wang;Huihui Kong;Bingxin Chu;Qian Yang;Chaohui Lin;Rui Liu;Changxu Chen;Yang Gao;Guojun Wang;Dayan Wang;Chen Qin;Xiaohua Ye;Lifei Yu;Xiangfei Xu;Jie Jin;Ren Sun;Hualan Chen;Xudong Wu;Zeli Zhang
作者机构:
关键词: broad-inhibition antibody;influenza virus;memory B cells;neuraminidase;pre-existing immunity
期刊名称: Cell Host and Microbe
ISSN: 1931-3128
年卷期: 2025 年 33 卷 1 期
页码:
收录情况: SCIE(2025版)
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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