9C0X

Crystal structure of chimeric hemagglutinin cH11/1 in complex with broad protective antibody 31.b.09

Summary for 9C0X

• Entry DOI: 10.2210/pdb9c0x/pdb
• Descriptor: Hemagglutinin HA2 subunit, Antibody 31.b.09 Fab light chain, Antibody 31.b.09 Fab heavy chain, ... (6 entities in total)
• Functional Keywords: immune system, viral protein-immune system complex, viral protein/immune system
• Biological source: Influenza A virus; More
• Total number of polymer chains: 4
• Total formula weight: 81287.78

Authors

Nguyen, T.K.Y.,Zhu, X.,Wilson, I.A. (deposition date: 2024-05-28, release date: 2025-05-07, Last modification date: 2025-05-28)

Primary citation

Nguyen, Y.T.K.,Zhu, X.,Han, J.,Rodriguez, A.J.,Sun, W.,Yu, W.,Palese, P.,Krammer, F.,Ward, A.B.,Wilson, I.A.
Structural characterization of influenza group 1 chimeric hemagglutinins as broad vaccine immunogens.
Proc.Natl.Acad.Sci.USA, 122:e2416628122-e2416628122, 2025

PubMed Abstract: Chimeric hemagglutinins (cHA) appear to be promising for the design and development of universal influenza vaccines. Influenza A group 1 cHAs, cH5/1, cH8/1, and cH11/1, comprising an H1 stem attached to either an H5, H8, or H11 globular head, have been used sequentially as vaccine immunogens in human clinical trials and induced high levels of broadly protective antibodies. Using X-ray crystallography and negative-stain electron microscopy, we determined structures of cH5/1, cH8/1, and cH11/1 HAs in their apo (unliganded) and antibody Fab-bound states. Stem-reactive antibodies 3E1 and 31.b.09 recognize their cognate epitopes in cH5/1, cH8/1, and cH11/1 HAs. However, with cH5/1, the head domains are rotated by 35 to 45° around the threefold axis of the HA trimer compared to native HA with a more splayed-open conformation at the stem base. cH11/1 with 3E1 is structurally more native-like but resembles cH5/1 with 31.b.09, whereas cH8/1 with 31.b.09 exhibited a range of closed-to-open stem configurations with some separation of head and stem domains. Furthermore, all of these group 1 cHAs effectively bound a broad head trimer interface antibody and other broad stem antibodies. Thus, the cHAs exhibit structural plasticity without compromising the stem and head trimer interface epitopes for elicitation of influenza A group 1 cross-reactive antibodies.

PubMed: 39937865
DOI: 10.1073/pnas.2416628122

Experimental method

X-RAY DIFFRACTION (4.35 Å)