Human monoclonal antibodies isolated after seasonal vaccination broadly neutralize antigenically drifted influenza B viruses

IF 23.2 1区医学 Q1 MICROBIOLOGY

Cell host & microbe Pub Date : 2026-03-20 DOI:10.1016/j.chom.2026.02.018

Xiaoyu Cai, Miao Fan, Yanmei Zhai, Wanyu Luo, Shuning Liu, Kexin Lv, Min Zhao, Lin Liu, Siwei Zhou, Mengxin Xu, Bing He, Yuzhu Sun, Ruixin Zhao, Xingchen Zhu, Yu Kuang, Hongjie Lu, Xinyu Yue, Kuibiao Li, Yu Zhang, Li Yuan, Yao-Qing Chen

{"title":"Human monoclonal antibodies isolated after seasonal vaccination broadly neutralize antigenically drifted influenza B viruses","authors":"Xiaoyu Cai, Miao Fan, Yanmei Zhai, Wanyu Luo, Shuning Liu, Kexin Lv, Min Zhao, Lin Liu, Siwei Zhou, Mengxin Xu, Bing He, Yuzhu Sun, Ruixin Zhao, Xingchen Zhu, Yu Kuang, Hongjie Lu, Xinyu Yue, Kuibiao Li, Yu Zhang, Li Yuan, Yao-Qing Chen","doi":"10.1016/j.chom.2026.02.018","DOIUrl":null,"url":null,"abstract":"Antigenic drift in hemagglutinin (HA) enables influenza viruses to escape host immunity. Elucidating molecular features of antigenic drift is essential for updating seasonal vaccines and pandemic preparedness. Here, we found that influenza B viruses (IBVs) isolated after 2019 escaped neutralization by several previously identified broadly neutralizing monoclonal antibodies (bnAbs). Meanwhile, we identified two IBV bnAbs, CAV-CF22 and CAV-CH76, isolated via quadrivalent vaccine. They exhibited broad neutralizing activity against Victoria- and Yamagata-lineage viruses <em>in vitro</em> and protected <em>in vivo</em> against contemporary Victoria and Yamagata strains. Phylogenetic and structural analysis revealed fixation of K136E in post-2019 Victoria HA, disrupting epitopes targeted by most previously characterized head-directed IBV-monoclonal antibodies (mAbs). High-resolution structures reveal that, rather than engaging K136, CAV-CF22 and CAV-CH76 insert HCDR3 into the receptor-binding site (RBS) to sterically mimic sialic acid. The conservation of epitope residues underlies the antibodies’ broad neutralizing activity against IBV and informs antibody- and vaccine-design strategies that are resilient to recent IBV drift.","PeriodicalId":9693,"journal":{"name":"Cell host & microbe","volume":"10 1","pages":""},"PeriodicalIF":23.2000,"publicationDate":"2026-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell host & microbe","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.chom.2026.02.018","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MICROBIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Antigenic drift in hemagglutinin (HA) enables influenza viruses to escape host immunity. Elucidating molecular features of antigenic drift is essential for updating seasonal vaccines and pandemic preparedness. Here, we found that influenza B viruses (IBVs) isolated after 2019 escaped neutralization by several previously identified broadly neutralizing monoclonal antibodies (bnAbs). Meanwhile, we identified two IBV bnAbs, CAV-CF22 and CAV-CH76, isolated via quadrivalent vaccine. They exhibited broad neutralizing activity against Victoria- and Yamagata-lineage viruses in vitro and protected in vivo against contemporary Victoria and Yamagata strains. Phylogenetic and structural analysis revealed fixation of K136E in post-2019 Victoria HA, disrupting epitopes targeted by most previously characterized head-directed IBV-monoclonal antibodies (mAbs). High-resolution structures reveal that, rather than engaging K136, CAV-CF22 and CAV-CH76 insert HCDR3 into the receptor-binding site (RBS) to sterically mimic sialic acid. The conservation of epitope residues underlies the antibodies’ broad neutralizing activity against IBV and informs antibody- and vaccine-design strategies that are resilient to recent IBV drift.

Abstract Image

查看原文本刊更多论文

季节性疫苗接种后分离的人单克隆抗体广泛中和抗原漂移的乙型流感病毒

血凝素（HA）中的抗原漂移使流感病毒能够逃避宿主免疫。阐明抗原漂移的分子特征对于更新季节性疫苗和预防大流行至关重要。在这里，我们发现2019年之后分离的乙型流感病毒（ibv）逃脱了先前鉴定的几种广泛中和的单克隆抗体（bnAbs）的中和。同时，我们通过四价疫苗分离出了两种IBV单克隆抗体CAV-CF22和CAV-CH76。它们在体外对维多利亚和山形病毒表现出广泛的中和活性，在体内对当代维多利亚和山形病毒株具有保护作用。系统发育和结构分析显示，K136E在2019年后的Victoria HA中固定，破坏了大多数先前鉴定的头部定向ibv单克隆抗体（mab）靶向的表位。高分辨率结构显示，CAV-CF22和CAV-CH76将HCDR3插入受体结合位点（RBS）以立体模拟唾液酸，而不是与K136结合。表位残基的保守性奠定了抗体对IBV广泛中和活性的基础，并为抗体和疫苗设计策略提供了信息，以适应最近IBV的漂移。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

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.