8TP7

H2 hemagglutinin (A/Singapore/1/1957) in complex with Sa-targeting Fab 4-1-1G03

Summary for 8TP7

• Entry DOI: 10.2210/pdb8tp7/pdb
• EMDB information: 41469
• Descriptor: Hemagglutinin, Heavy chain of monoclonal antibody 4-1-1G03, Light chain of monoclonal antibody 4-1-1G03, ... (5 entities in total)
• Functional Keywords: influenza, hemagglutinin, monoclonal antibody, immune complex, viral protein, viral protein-immune system complex, viral protein/immune system
• Biological source: Influenza A virus (A/Singapore/1/1957(H2N2)); More
• Total number of polymer chains: 9
• Total formula weight: 268671.81

Authors

Yang, Y.R.,Han, J.,Perrett, H.R.,Ward, A.B. (deposition date: 2023-08-04, release date: 2023-10-11, Last modification date: 2024-11-20)

Primary citation

Yang, Y.R.,Han, J.,Perrett, H.R.,Richey, S.T.,Jackson, A.M.,Rodriguez, A.J.,Gillespie, R.A.,O'Connell, S.,Raab, J.E.,Cominsky, L.Y.,Chopde, A.,Kanekiyo, M.,Houser, K.V.,Chen, G.L.,McDermott, A.B.,Andrews, S.F.,Ward, A.B.
Immune memory shapes human polyclonal antibody responses to H2N2 vaccination.
Biorxiv, 2023

PubMed Abstract: Influenza A virus subtype H2N2, which caused the 1957 influenza pandemic, remains a global threat. A recent phase I clinical trial investigating a ferritin nanoparticle displaying H2 hemagglutinin in H2-naïve and H2-exposed adults. Therefore, we could perform comprehensive structural and biochemical characterization of immune memory on the breadth and diversity of the polyclonal serum antibody response elicited after H2 vaccination. We temporally map the epitopes targeted by serum antibodies after first and second vaccinations and show previous H2 exposure results in higher responses to the variable head domain of hemagglutinin while initial responses in H2-naïve participants are dominated by antibodies targeting conserved epitopes. We use cryo-EM and monoclonal B cell isolation to describe the molecular details of cross-reactive antibodies targeting conserved epitopes on the hemagglutinin head including the receptor binding site and a new site of vulnerability deemed the medial junction. Our findings accentuate the impact of pre-existing influenza exposure on serum antibody responses.

PubMed: 37781590
DOI: 10.1101/2023.08.23.554525

Experimental method

ELECTRON MICROSCOPY (2.8 Å)