Structural insights into the broad protection against H1 influenza viruses by a computationally optimized hemagglutinin vaccine

• DOI: 10.1038/s42003-023-04793-3
• Publication Date: 2023-04-25T07:02:56Z
• Authors: John V. Dzimianski; Julianna Han; Giuseppe A. Sautto; Sara M. O’Rourke; Joseph M. Cruz; Spencer R. Pierce; Jeffrey W. Ecker; Michael A. Carlock; Kaito A. Nagashima; Jarrod J. Mousa; Ted M. Ross; Andrew B. Ward; Rebecca M. DuBois
• Keywords: Cobra

Influenza virus poses an ongoing human health threat with pandemic potential. Due to mutations in circulating strains, formulating effective vaccines remains a challenge. The use of computationally optimized broadly reactive antigen (COBRA) hemagglutinin (HA) proteins is promising vaccine strategy protect against wide range current and future influenza viruses. Though preclinical studies, the mechanistic basis driving broad reactivity COBRA be elucidated. Here, we report crystal structure HA termed P1 identify antigenic glycosylation properties that contribute its immunogenicity. We further cryo-EM P1-elicited neutralizing antibody 1F8 bound P1, revealing recognize atypical receptor binding site epitope via unexpected mode binding.