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

IF 20.6 1区医学 Q1 MICROBIOLOGY

Cell host & microbe Pub Date : 2024-12-30 DOI:10.1016/j.chom.2024.12.004

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

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引用次数: 0

Abstract

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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预先存在的记忆B细胞中广泛抑制流感神经氨酸酶抗体的鉴定

识别广泛反应的B前体细胞和保守的表位对于开发通用流感疫苗至关重要。在这项研究中，使用流感神经氨酸酶（NA）突变探针，我们发现人类预先存在的NA特异性记忆B细胞（MBCs）占总MBCs的约0.25%，这些MBCs是异质的，由未切换的MBCs主导。此外，我们鉴定了三种NA广泛抑制单克隆抗体（单克隆抗体）（BImAbs），它们阻断来自不同流感毒株的NA的活性，包括最近的牛H5N1。低温电镜（cryo-EM）结构显示，BImAb靶向保守的NA酶袋和邻近NA单体的单独表位。此外，NA BImAbs保护小鼠免受人类大流行H1N1和H5N1的致命挑战。我们的研究表明，NA广泛抑制前体MBCs存在于健康成人中，可以作为基于NA的通用流感疫苗的靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cell host & microbe 生物-微生物学

CiteScore

45.10

自引率

1.70%

发文量

201

审稿时长

4-8 weeks

期刊介绍： Cell Host & Microbe is a scientific journal that was launched in March 2007. The journal aims to provide a platform for scientists to exchange ideas and concepts related to the study of microbes and their interaction with host organisms at a molecular, cellular, and immune level. It publishes novel findings on a wide range of microorganisms including bacteria, fungi, parasites, and viruses. The journal focuses on the interface between the microbe and its host, whether the host is a vertebrate, invertebrate, or plant, and whether the microbe is pathogenic, non-pathogenic, or commensal. The integrated study of microbes and their interactions with each other, their host, and the cellular environment they inhabit is a unifying theme of the journal. The published work in Cell Host & Microbe is expected to be of exceptional significance within its field and also of interest to researchers in other areas. In addition to primary research articles, the journal features expert analysis, commentary, and reviews on current topics of interest in the field.