7U8J

Crystal structure of chimeric hemagglutinin cH4/3 in complex with broad protective antibody 31.a.83

Summary for 7U8J

• Entry DOI: 10.2210/pdb7u8j/pdb
• Descriptor: Hemagglutinin HA1 subunit, Hemagglutinin HA2 subunit, Antibody Fab light chain, ... (4 entities in total)
• Functional Keywords: universal vaccine design, chimeric influenza hemagglutinin, ha trimer interface and stem, viral protein-immune system complex, viral protein/immune system
• Biological source: Influenza A virus; More
• Total number of polymer chains: 4
• Total formula weight: 104591.69

Authors

Zhu, X.,Wilson, I.A. (deposition date: 2022-03-08, release date: 2022-06-08, Last modification date: 2024-10-23)

Primary citation

Zhu, X.,Han, J.,Sun, W.,Puente-Massaguer, E.,Yu, W.,Palese, P.,Krammer, F.,Ward, A.B.,Wilson, I.A.
Influenza chimeric hemagglutinin structures in complex with broadly protective antibodies to the stem and trimer interface.
Proc.Natl.Acad.Sci.USA, 119:e2200821119-e2200821119, 2022

PubMed Abstract: Influenza virus hemagglutinin (HA) has been the primary target for influenza vaccine development. Broadly protective antibodies targeting conserved regions of the HA unlock the possibility of generating universal influenza immunity. Two group 2 influenza A chimeric HAs, cH4/3 and cH15/3, were previously designed to elicit antibodies to the conserved HA stem. Here, we show by X-ray crystallography and negative-stain electron microscopy that a broadly protective antistem antibody can stably bind to cH4/3 and cH15/3 HAs, thereby validating their potential as universal vaccine immunogens. Furthermore, flexibility was observed in the head domain of the chimeric HA structures, suggesting that antibodies could also potentially interact with the head interface epitope. Our structural and binding studies demonstrated that a broadly protective antihead trimeric interface antibody could indeed target the more open head domain of the cH15/3 HA trimer. Thus, in addition to inducing broadly protective antibodies against the conserved HA stem, chimeric HAs may also be able to elicit antibodies against the conserved trimer interface in the HA head domain, thereby increasing the vaccine efficacy.

PubMed: 35594401
DOI: 10.1073/pnas.2200821119

Experimental method

X-RAY DIFFRACTION (4.9 Å)