8tp5 | pdb_00008tp5
H1 hemagglutinin (NC99) in complex with RBS-targeting Fab 1-1-1E04
Structural highlights
FunctionQ6WG00_9INFA Binds to sialic acid-containing receptors on the cell surface, bringing about the attachment of the virus particle to the cell. This attachment induces virion internalization of about two third of the virus particles through clathrin-dependent endocytosis and about one third through a clathrin- and caveolin-independent pathway. Plays a major role in the determination of host range restriction and virulence. Class I viral fusion protein. Responsible for penetration of the virus into the cell cytoplasm by mediating the fusion of the membrane of the endocytosed virus particle with the endosomal membrane. Low pH in endosomes induces an irreversible conformational change in HA2, releasing the fusion hydrophobic peptide. Several trimers are required to form a competent fusion pore (By similarity).[SAAS:SAAS00204388] Publication Abstract from PubMedInfluenza 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-naive 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-naive 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. HIGHLIGHTS: Serum Abs after first H2-F vaccination in H2-exposed donors bound variable HA head epitopesSerum Abs after first H2-F vaccination in H2-naive donors bound conserved HA head and stem epitopesRBS-targeting VH1-69 cross-reactive antibodies were induced in H2-naive individualsThe medial junction is a previously uncharacterized conserved epitope on the HA head. Immune memory shapes human polyclonal antibody responses to H2N2 vaccination.,Yang YR, Han J, Perrett HR, Richey ST, Jackson AM, Rodriguez AJ, Gillespie RA, O'Connell S, Raab JE, Cominsky LY, Chopde A, Kanekiyo M, Houser KV, Chen GL, McDermott AB, Andrews SF, Ward AB bioRxiv. 2023 Aug 24:2023.08.23.554525. doi: 10.1101/2023.08.23.554525. Preprint. PMID:37781590[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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