Antibody recognition of the pandemic H1N1 Influenza virus hemagglutinin receptor binding site.

Hong M, Lee PS, Hoffman RM, Zhu X, Krause JC, Laursen NS, Yoon SI, Song L, Tussey L, Crowe JE, Ward AB, Wilson IA
J Virol. 2013 87 (22): 12471-80

PMID: 24027321 · PMCID: PMC3807900 · DOI:10.1128/JVI.01388-13

Influenza virus is a global health concern due to its unpredictable pandemic potential. This potential threat was realized in 2009 when an H1N1 virus emerged that resembled the 1918 virus in antigenicity but fortunately was not nearly as deadly. 5J8 is a human antibody that potently neutralizes a broad spectrum of H1N1 viruses, including the 1918 and 2009 pandemic viruses. Here, we present the crystal structure of 5J8 Fab in complex with a bacterially expressed and refolded globular head domain from the hemagglutinin (HA) of the A/California/07/2009 (H1N1) pandemic virus. 5J8 recognizes a conserved epitope in and around the receptor binding site (RBS), and its HCDR3 closely mimics interactions of the sialic acid receptor. Electron microscopy (EM) reconstructions of 5J8 Fab in complex with an HA trimer from a 1986 H1 strain and with an engineered stabilized HA trimer from the 2009 H1 pandemic virus showed a similar mode of binding. As for other characterized RBS-targeted antibodies, 5J8 uses avidity to extend its breadth and affinity against divergent H1 strains. 5J8 selectively interacts with HA insertion residue 133a, which is conserved in pandemic H1 strains and has precluded binding of other RBS-targeted antibodies. Thus, the RBS of divergent HAs is targeted by 5J8 and adds to the growing arsenal of common recognition motifs for design of therapeutics and vaccines. Moreover, consistent with previous studies, the bacterially expressed H1 HA properly refolds, retaining its antigenic structure, and presents a low-cost and rapid alternative for engineering and manufacturing candidate flu vaccines.

MeSH Terms (14)

Antibodies, Viral Antibody Affinity Antigens, Viral Binding Sites, Antibody Crystallography, X-Ray Hemagglutinin Glycoproteins, Influenza Virus Humans Influenza, Human Influenza A Virus, H1N1 Subtype Models, Molecular Pandemics Protein Conformation Receptors, Virus United States

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