9LHO

CryoEM structure of H7 hemagglutinin in complex with a human neutralizing antibody 6Y13

Summary for 9LHO

• Entry DOI: 10.2210/pdb9lho/pdb
• EMDB information: 63103
• Descriptor: Hemagglutinin, scFv of 6Y13 chimera, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• Functional Keywords: viral protein
• Biological source: Influenza A virus (A/duck/Chiba/25-51-14/2013(H7N1)); More
• Total number of polymer chains: 12
• Total formula weight: 510096.43

Authors

Wang, M.,Yuan, B.,Peng, Q.,Gao, G.F.,Shi, Y. (deposition date: 2025-01-13, release date: 2025-12-03)

Primary citation

Li, J.,Wang, M.,Yang, Y.,Zhang, L.,Liu, L.,Yang, W.,Peng, Y.,Zhang, X.,Yuan, B.,Peng, Q.,Yang, X.,Chen, Y.,Gao, G.F.,Shi, Y.,Wan, X.
Structural basis for a potent human neutralizing antibody targeting a conserved epitope on the H7 hemagglutinin head.
Proc.Natl.Acad.Sci.USA, 122:e2503008122-e2503008122, 2025

PubMed 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 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.

PubMed: 41196357
DOI: 10.1073/pnas.2503008122

Experimental method

ELECTRON MICROSCOPY (3.1 Å)