9E6J

DH726-1 Fab bound to hemagglutinin from influenza A/Solomon Islands/3/2006

Summary for 9E6J

• Entry DOI: 10.2210/pdb9e6j/pdb
• EMDB information: 47570
• Descriptor: Hemagglutinin, DH726-1 Fab heavy chain, DH726-1 Fab light chain (3 entities in total)
• Functional Keywords: immunoglobulin, antibody, viral protein, viral protein-immune system complex, viral protein/immune system
• Biological source: Alphainfluenzavirus influenzae; More
• Total number of polymer chains: 9
• Total formula weight: 321328.58

Authors

Finney, J.,Harrison, S.C. (deposition date: 2024-10-30, release date: 2026-01-21, Last modification date: 2026-08-12)

Primary citation

Gu, S.,Finney, J.,Luo, K.,Valencia, S.M.,Mielke, D.,Von Holle, T.A.,Marshall, D.J.,Parks, R.,Sutherland, L.L.,Scearce, R.M.,Wiehe, K.,Santra, S.,Harris, S.,DuVall, J.,Landon, C.D.,Spurrier, M.A.,Heaton, N.S.,Yassine, H.M.,Graham, B.S.,Kepler, T.B.,Liao, H.X.,Schmidt, A.G.,Ferrari, G.,Haynes, B.F.,Harrison, S.C.,Moody, M.A.
Elicitation of stem-directed antibodies in rhesus macaques by a conventional hemagglutinin immunogen.
Biorxiv, 2026

PubMed Abstract: Because they can bind many strains of influenza, antibodies targeting the hemagglutinin (HA) stem have been attractive targets for vaccine development. Many monoclonal antibodies (mAbs) directed at the HA stem have been isolated from humans, and these mAbs have mediated broad protection in animal models. We describe here HA stem-directed mAbs isolated from rhesus macaques immunized with an "ordinary" H1 HA trimer. All immunized rhesus macaques developed high serum titers with broad reactivity to diverse H1N1 and H5N1 viruses, and 7 isolated mAbs strongly blocked canonical stem antibody CR6261 binding to H1. MAb DH726.1 robustly protected mice from lethal challenge with H1N1 and H5N1 viruses, and cryo-EM showed the binding footprint overlapped that of some human mAbs. These findings suggest that vaccination with the standard, trimeric HA immunogens may be sufficient to elicit stem antibodies at titers adequate to protect against zoonotic H5N1 influenza.

PubMed: 42539121
DOI: 10.64898/2026.07.16.738984

Experimental method

ELECTRON MICROSCOPY (2.98 Å)