Structure-based Design of Chimeric Influenza Hemagglutinins to Elicit Cross-group Immunity.

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

SUBMITTER: Castro KM 

PROVIDER: S-EPMC11870435 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature