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Cell Host Microbe
. 2026 Mar 20:S1931-3128(26)00086-7.
doi: 10.1016/j.chom.2026.02.018. Online ahead of print.
Human monoclonal antibodies isolated after seasonal vaccination broadly neutralize antigenically drifted influenza B viruses
Xiaoyu Cai 1 , Miao Fan 2 , Yanmei Zhai 1 , Wanyu Luo 1 , Shuning Liu 1 , Kexin Lv 1 , Min Zhao 2 , Lin Liu 1 , Siwei Zhou 1 , Mengxin Xu 1 , Bing He 1 , Yuzhu Sun 1 , Ruixin Zhao 1 , Xingchen Zhu 1 , Yu Kuang 1 , Hongjie Lu 1 , Xinyu Yue 1 , Kuibiao Li 3 , Yu Zhang 4 , Li Yuan 4 , Na Zhou 4 , Feng Ye 4 , Huan Liang 5 , Yiyun Chen 3 , Min Zheng 6 , Zhangyong Hong 7 , Dayan Wang 8 , Zeli Zhang 9 , Yue-Long Shu 10 , Jiwan Ge 11 , Yao-Qing Chen 12
Affiliations
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.
Keywords: antigenic drift; broad neutralization; hemagglutinin; influenza B virus; monoclonal antibody; seasonal vaccine.
. 2026 Mar 20:S1931-3128(26)00086-7.
doi: 10.1016/j.chom.2026.02.018. Online ahead of print.
Human monoclonal antibodies isolated after seasonal vaccination broadly neutralize antigenically drifted influenza B viruses
Xiaoyu Cai 1 , Miao Fan 2 , Yanmei Zhai 1 , Wanyu Luo 1 , Shuning Liu 1 , Kexin Lv 1 , Min Zhao 2 , Lin Liu 1 , Siwei Zhou 1 , Mengxin Xu 1 , Bing He 1 , Yuzhu Sun 1 , Ruixin Zhao 1 , Xingchen Zhu 1 , Yu Kuang 1 , Hongjie Lu 1 , Xinyu Yue 1 , Kuibiao Li 3 , Yu Zhang 4 , Li Yuan 4 , Na Zhou 4 , Feng Ye 4 , Huan Liang 5 , Yiyun Chen 3 , Min Zheng 6 , Zhangyong Hong 7 , Dayan Wang 8 , Zeli Zhang 9 , Yue-Long Shu 10 , Jiwan Ge 11 , Yao-Qing Chen 12
Affiliations
- PMID: 41864199
- DOI: 10.1016/j.chom.2026.02.018
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.
Keywords: antigenic drift; broad neutralization; hemagglutinin; influenza B virus; monoclonal antibody; seasonal vaccine.