Human neutralizing antibodies target a conserved lateral patch on H7N9 hemagglutinin head

Manxue 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 () and Xueling Wu ()
Additional contact information
Manxue Jia: Columbia University Vagelos College of Physicians and Surgeons
Hanjun Zhao: University of Hong Kong
Nicholas C. Morano: Columbia University Vagelos College of Physicians and Surgeons
Hong Lu: Columbia University Vagelos College of Physicians and Surgeons
Yin-Ming Lui: University of Hong Kong
Haijuan Du: National Institutes of Health
Jordan E. Becker: Columbia University Vagelos College of Physicians and Surgeons
Kwok-Yung Yuen: University of Hong Kong
David D. Ho: Columbia University Vagelos College of Physicians and Surgeons
Peter D. Kwong: Columbia University Vagelos College of Physicians and Surgeons
Lawrence Shapiro: Columbia University Vagelos College of Physicians and Surgeons
Kelvin Kai-Wang To: University of Hong Kong
Xueling Wu: Columbia University Vagelos College of Physicians and Surgeons

Nature Communications, 2024, vol. 15, issue 1, 1-14

Abstract: 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.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-024-48758-4 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48758-4

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-48758-4

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().