Structural basis for a potent human neutralizing antibody targeting a conserved epitope on the H7 hemagglutinin head

Zoonotic H7N9 avian influenza virus infection remains a global concern because of its pandemic potential. Therefore, developing effective antibodies and vaccines against H7N9 is vital for preventing and controlling major outbreaks. Here, we isolated a human <i>VH3-30</i> gene-encoded antibody, designated 6Y13, from a survivor of H7N9 infection. This antibody recognized the hemagglutinins (HAs) of the representative H7 subtype zoonotic viruses spanning two decades of antigenic evolution and potently neutralized epidemic H7N9 viruses in vitro. Moreover, 6Y13 conferred complete protection in mice against lethal H7N9 challenge in both prophylactic and therapeutic experiments. Structural analysis by cryoelectron microscopy indicated that 6Y13 binds to a unique conserved site on the HA head, distinct from the receptor-binding site and lateral patch. Nevertheless, 6Y13 efficiently blocked viral receptor binding without interfering with HA receptor binding, independent of Fc-mediated steric hindrance. Our findings provide a promising therapeutic candidate against pan-H7 subtype viruses and are beneficial for the design of H7 subtype influenza vaccine immunogens.

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Publication Details

Journal
Proceedings of the National Academy of Sciences
Published
2025-11-06
DOI
https://doi.org/10.1073/pnas.2503008122
Primary Topic
Influenza Virus Research Studies
Type
article
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article

Structural basis for a potent human neutralizing antibody targeting a conserved epitope on the H7 hemagglutinin head

Lvyan Liu, George F. Gao, Junxin Li, Xiaolu Yang et al.
Proceedings of the National Academy of Sciences
Influenza Virus Research Studies
article

Structural basis for a potent human neutralizing antibody targeting a conserved epitope on the H7 hemagglutinin head

Lvyan Liu, George F. Gao, Junxin Li, Xiaolu Yang, Yi Shi, Bin Yuan, Qi Peng, Yixin Chen, Yang Yang, Limin Zhang, Min Wang, Xu Zhang, Wei Yang, Yun Peng, Xiaochun Wan
article en

Abstract

Zoonotic H7N9 avian influenza virus infection remains a global concern because of its pandemic potential. Therefore, developing effective antibodies and vaccines against H7N9 is vital for preventing and controlling major outbreaks. Here, we isolated a human <i>VH3-30</i> gene-encoded antibody, designated 6Y13, from a survivor of H7N9 infection. This antibody recognized the hemagglutinins (HAs) of the representative H7 subtype zoonotic viruses spanning two decades of antigenic evolution and potently neutralized epidemic H7N9 viruses in vitro. Moreover, 6Y13 conferred complete protection in mice against lethal H7N9 challenge in both prophylactic and therapeutic experiments. Structural analysis by cryoelectron microscopy indicated that 6Y13 binds to a unique conserved site on the HA head, distinct from the receptor-binding site and lateral patch. Nevertheless, 6Y13 efficiently blocked viral receptor binding without interfering with HA receptor binding, independent of Fc-mediated steric hindrance. Our findings provide a promising therapeutic candidate against pan-H7 subtype viruses and are beneficial for the design of H7 subtype influenza vaccine immunogens.

Proceedings of the National Academy of SciencesVol. 122(45)
ActionAid (US), Cancer Research Institute (US), Xiamen University (CN), Chinese Academy of Sciences (CN), Southern University of Science and Technology (CN), Guangzhou Experimental Station (CN), First Affiliated Hospital of Guangzhou Medical University (CN), Institute of Microbiology (BY), Shenzhen Maternity and Child Healthcare Hospital (CN), Czech Academy of Sciences, Institute of Microbiology (CZ), UPMC Hillman Cancer Center (US), Institute of Microbiology (CN), Shenzhen Institutes of Advanced Technology (CN), Shenzhen Second People's Hospital (CN), University of Chinese Academy of Sciences (CN), Shenzhen Third People’s Hospital (CN), University of Pennsylvania (US), Guangzhou Medical University (CN)
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Influenza Virus Research Studies
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