8TNL

CryoEM structure of H7 hemagglutinin from A/Shanghai2/2013 H7N9 in complex with a human neutralizing antibody H7.HK1

Summary for 8TNL

• Entry DOI: 10.2210/pdb8tnl/pdb
• EMDB information: 41422
• Descriptor: H7.HK1 Neutralizing Antibody Heavy Chain, Hemagglutinin, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• Functional Keywords: virus, antibody, influenza, viral protein, viral protein-immune system complex, viral protein/immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 9
• Total formula weight: 265805.33

Authors

Morano, N.C.,Wu, X.,Shapiro, L. (deposition date: 2023-08-02, release date: 2024-05-15, Last modification date: 2024-09-04)

Primary citation

Jia, M.,Zhao, H.,Morano, N.C.,Lu, H.,Lui, Y.M.,Du, H.,Becker, J.E.,Yuen, K.Y.,Ho, D.D.,Kwong, P.D.,Shapiro, L.,To, K.K.,Wu, X.
Human neutralizing antibodies target a conserved lateral patch on H7N9 hemagglutinin head.
Nat Commun, 15:4505-4505, 2024

PubMed Abstract: Avian influenza A virus H7N9 causes severe human infections with >30% fatality. Currently, there is no H7N9-specific prevention or treatment for humans. Here, from a 2013 H7N9 convalescent case in Hong Kong, we isolate four hemagglutinin (HA)-reactive monoclonal antibodies (mAbs), with three directed to the globular head domain (HA1) and one to the stalk domain (HA2). Two clonally related HA1-directed mAbs, H7.HK1 and H7.HK2, potently neutralize H7N9 and protect female mice from lethal H7N9/AH1 challenge. Cryo-EM structures reveal that H7.HK1 and H7.HK2 bind to a β14-centered surface and disrupt the 220-loop that makes hydrophobic contacts with sialic acid on an adjacent protomer, thereby blocking viral entry. Sequence analysis indicates the lateral patch targeted by H7.HK1 and H7.HK2 to be conserved among influenza subtypes. Both H7.HK1 and H7.HK2 retain HA1 binding and neutralization capacity to later H7N9 isolates from 2016-2017, consistent with structural data showing that the antigenic mutations during this timeframe occur at their epitope peripheries. The HA2-directed mAb H7.HK4 lacks neutralizing activity but when used in combination with H7.HK2 moderately augments female mouse protection. Overall, our data reveal antibodies to a conserved lateral HA1 supersite that confer neutralization, and when combined with a HA2-directed non-neutralizing mAb, augment protection.

PubMed: 38802413
DOI: 10.1038/s41467-024-48758-4

Experimental method

ELECTRON MICROSCOPY (3.62 Å)