Structural basis of broad protection against influenza virus by human antibodies targeting the neuraminidase active site via a recurring motif in CDR H3

Gyunghee Jo, Seiya Yamayoshi, Krystal M. Ma, Olivia Swanson, Jonathan L. Torres, James A. Ferguson, Monica L. Fernández-Quintero, Jiachen Huang, Jeffrey Copps, Alesandra J. Rodriguez, Jon M. Steichen, Yoshihiro Kawaoka, Julianna Han () and Andrew B. Ward ()
Additional contact information
Gyunghee Jo: The Scripps Research Institute
Seiya Yamayoshi: The University of Tokyo
Krystal M. Ma: The Scripps Research Institute
Olivia Swanson: The Scripps Research Institute
Jonathan L. Torres: The Scripps Research Institute
James A. Ferguson: The Scripps Research Institute
Monica L. Fernández-Quintero: The Scripps Research Institute
Jiachen Huang: The Scripps Research Institute
Jeffrey Copps: The Scripps Research Institute
Alesandra J. Rodriguez: The Scripps Research Institute
Jon M. Steichen: The Scripps Research Institute
Yoshihiro Kawaoka: The University of Tokyo
Julianna Han: The Scripps Research Institute
Andrew B. Ward: The Scripps Research Institute

Nature Communications, 2025, vol. 16, issue 1, 1-16

Abstract: Abstract Influenza viruses evolve rapidly, driving seasonal epidemics and posing global pandemic threats. While neuraminidase (NA) has emerged as a vaccine target, shared molecular features of NA antibody responses are still not well understood. Here, we describe cryo-electron microscopy structures of the broadly protective human antibody DA03E17, which was previously identified from an H1N1-infected donor, in complex with NA from A/H1N1, A/H3N2, and B/Victoria-lineage viruses. DA03E17 targets the highly conserved NA active site using its long CDR H3, which features a DR (Asp–Arg) motif that engages catalytic residues and mimics sialic acid interactions. We further demonstrate that this motif is conserved among several NA active site-targeting antibodies, indicating a common receptor mimicry strategy. We also identified BCR sequences containing this DR motif across all donors in a healthy human repertoire database, suggesting that such precursors may be relatively common and have vaccine targeting potential. Our findings reveal shared molecular features in NA active site-targeting antibodies that can be harnessed to design broad, immune-focused influenza vaccines.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-62174-2 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:16:y:2025:i:1:d:10.1038_s41467-025-62174-2

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

DOI: 10.1038/s41467-025-62174-2

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 ().