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TitleHuman neutralizing antibodies target a conserved lateral patch on H7N9 hemagglutinin head.
Journal, issue, pagesNat Commun, Vol. 15, Issue 1, Page 4505, Year 2024
Publish dateMay 27, 2024
AuthorsManxue Jia / Hanjun Zhao / Nicholas C Morano / Hong Lu / Yin-Ming Lui / Haijuan Du / Jordan E Becker / Kwok-Yung Yuen / David D Ho / Peter D Kwong / Lawrence Shapiro / Kelvin Kai-Wang To / Xueling Wu /
PubMed AbstractAvian 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 ...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.
External linksNat Commun / PubMed:38802413 / PubMed Central
MethodsEM (single particle)
Resolution3.62 - 3.69 Å
Structure data

41422

8tnl

EMDB-41422, PDB-8tnl:
CryoEM structure of H7 hemagglutinin from A/Shanghai2/2013 H7N9 in complex with a human neutralizing antibody H7.HK1
Method: EM (single particle) / Resolution: 3.62 Å

41441

8toa

EMDB-41441, PDB-8toa:
CryoEM structure of H7 hemagglutinin from A/Shanghai2/2013 H7N9 in complex with a human neutralizing antibody H7.HK2
Method: EM (single particle) / Resolution: 3.69 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

Source
  • homo sapiens (human)
  • influenza a virus (a/shanghai/02/2013(h7n9))
KeywordsVIRAL PROTEIN/IMMUNE SYSTEM / virus / antibody / influenza / VIRAL PROTEIN / VIRAL PROTEIN-IMMUNE SYSTEM complex

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