9MER

Structure of H1H5:FluA20 Chimeric Influenza HA Complex

Summary for 9MER

• Entry DOI: 10.2210/pdb9mer/pdb
• Descriptor: H1H5 HA, FluA20 Heavy Chain Fab, FluA20 Light Chain Fab, ... (8 entities in total)
• Functional Keywords: influenza, hemagglutinins, ha, chimera h1, h5, viral protein-immune system complex, viral protein/immune system
• Biological source: Influenza A virus; More
• Total number of polymer chains: 3
• Total formula weight: 76477.61

Authors

Seraj, N. (deposition date: 2024-12-08, release date: 2025-03-19)

Primary citation

Castro, K.M.,Ayardulabi, R.,Wehrle, S.,Cui, H.,Georgeon, S.,Schmidt, J.,Xiao, S.,Seraj, N.,Harshbarger, W.,Mallett, C.P.,Vassilev, V.,Saelens, X.,Correia, B.E.
Structure-based Design of Chimeric Influenza Hemagglutinins to Elicit Cross-group Immunity.
Biorxiv, 2025

PubMed Abstract: Antigenic variability among influenza virus strains poses a significant challenge to developing broadly protective, long-lasting vaccines. Current annual vaccines target specific strains, requiring accurate prediction for effective neutralization. Despite sequence diversity across phylogenetic groups, the hemagglutinin (HA) head domain's structure remains highly conserved. Utilizing this conservation, we designed cross-group chimeric HAs that combine antigenic surfaces from distant strains. By structure-guided transplantation of receptor-binding site (RBS) residues, we displayed an H3 RBS on an H1 HA scaffold. These chimeric immunogens elicit cross-group polyclonal responses capable of neutralizing both base and distal strains. Additionally, the chimeras integrate heterotrimeric immunogens, enhancing modular vaccine design. This approach enables the inclusion of diverse strain segments to generate broad polyclonal responses. In the future, such modular immunogens may serve as tools for evaluating immunodominance and refining immunization strategies, offering potential to bridge and enhance immune responses in individuals with pre-existing immunity. This strategy holds promise for advancing universal influenza vaccine development.

PubMed: 40027756
DOI: 10.1101/2024.12.17.628867

Experimental method

X-RAY DIFFRACTION (2 Å)