tetano
Editor, Senior Moderator
Cell Rep
. 2026 Oct 29;45(11):118180.
doi: 10.1016/j.celrep.2026.118180. Online ahead of print.
Huan Liang 1 , Chuanying Niu 2 , Yuanyi Cheng 1 , Kong Yen Liew 3 , Linbing Qu 2 , Zhiqiang Zheng 3 , Wenyi Yang 1 , Qian Wang 1 , Lang Wei 1 , Banghui Liu 2 , Fenhua Hu 1 , Chunxiao Xing 1 , Jiafang Chen 1 , Weiqi Pan 1 , Pingchao Li 2 , Yee-Joo Tan 4 , Xiaoli Xiong 5 , Ling Chen 6 , Xuefeng Niu 7
Affiliations Expand
Avian influenza viruses of the H5Nx subtype pose persistent pandemic threats. Here, we immunized rhesus macaques with an H5N6 vaccine and obtained 30 H5-reactive monoclonal antibodies (mAbs). Three IgG mAbs, 3CF5, 3BG3, and 3BE7, demonstrated potent neutralizing activity against multiple H5Nx viruses and conferred protection in a lethal mouse challenge model. Notably, 3CF5 exhibited broad neutralization against H5Nx viruses spanning 1997-2024, including contemporary clade 2.3.4.4b H5N1 strains associated with an ongoing outbreak in dairy cattle. Cryo-electron microscopy (cryo-EM) analysis revealed that 3CF5 targets a conserved non-receptor-binding epitope on the hemagglutinin (HA) head, spanning the vestigial esterase domain and an adjacent lateral surface. 3CF5 mediates neutralization primarily through inhibiting membrane fusion and also possesses antibody-dependent cellular cytotoxicity. Furthermore, isotype conversion of 3CF5-IgG to mucosal secretory IgA1 (sIgA1) enhanced neutralization potency against H5N1 viruses up to 128-fold, highlighting the advantage of sIgA1 as a nasally administered prophylactic agent.
Keywords: AIV; CP: microbiology; H5Nx; HA; avian influenza virus; broadly neutralizing antibody; hemagglutinin; mucosal secretory IgA; sIgA.
. 2026 Oct 29;45(11):118180.
doi: 10.1016/j.celrep.2026.118180. Online ahead of print.
Antibody 3CF5 neutralizes historical and emerging H5Nx influenza viruses by targeting a conserved non-receptor-binding hemagglutinin epitope
Huan Liang 1 , Chuanying Niu 2 , Yuanyi Cheng 1 , Kong Yen Liew 3 , Linbing Qu 2 , Zhiqiang Zheng 3 , Wenyi Yang 1 , Qian Wang 1 , Lang Wei 1 , Banghui Liu 2 , Fenhua Hu 1 , Chunxiao Xing 1 , Jiafang Chen 1 , Weiqi Pan 1 , Pingchao Li 2 , Yee-Joo Tan 4 , Xiaoli Xiong 5 , Ling Chen 6 , Xuefeng Niu 7
Affiliations Expand
- PMID: 42955944
- DOI: 10.1016/j.celrep.2026.118180
Abstract
Avian influenza viruses of the H5Nx subtype pose persistent pandemic threats. Here, we immunized rhesus macaques with an H5N6 vaccine and obtained 30 H5-reactive monoclonal antibodies (mAbs). Three IgG mAbs, 3CF5, 3BG3, and 3BE7, demonstrated potent neutralizing activity against multiple H5Nx viruses and conferred protection in a lethal mouse challenge model. Notably, 3CF5 exhibited broad neutralization against H5Nx viruses spanning 1997-2024, including contemporary clade 2.3.4.4b H5N1 strains associated with an ongoing outbreak in dairy cattle. Cryo-electron microscopy (cryo-EM) analysis revealed that 3CF5 targets a conserved non-receptor-binding epitope on the hemagglutinin (HA) head, spanning the vestigial esterase domain and an adjacent lateral surface. 3CF5 mediates neutralization primarily through inhibiting membrane fusion and also possesses antibody-dependent cellular cytotoxicity. Furthermore, isotype conversion of 3CF5-IgG to mucosal secretory IgA1 (sIgA1) enhanced neutralization potency against H5N1 viruses up to 128-fold, highlighting the advantage of sIgA1 as a nasally administered prophylactic agent.
Keywords: AIV; CP: microbiology; H5Nx; HA; avian influenza virus; broadly neutralizing antibody; hemagglutinin; mucosal secretory IgA; sIgA.