@article{ef457a3a8e1c4454a78100f07e067364,
title = "Structural and functional bases for broad-spectrum neutralization of avian and human influenza A viruses",
abstract = "Influenza virus remains a serious health threat, owing to its ability to evade immune surveillance through rapid genetic drift and reassortment. Here we used a human non-immune antibody phage-display library and the H5 hemagglutinin ectodomain to select ten neutralizing antibodies (nAbs) that were effective against all group 1 influenza viruses tested, including H5N1 'bird flu' and the H1N1 'Spanish flu'. The crystal structure of one such nAb bound to H5 shows that it blocks infection by inserting its heavy chain into a conserved pocket in the stem region, thus preventing membrane fusion. Nine of the nAbs employ the germline gene VH1-69, and all seem to use the same neutralizing mechanism. Our data further suggest that this region is recalcitrant to neutralization escape and that nAb-based immunotherapy is a promising strategy for broad-spectrum protection against seasonal and pandemic influenza viruses.",
author = "Jianhua Sui and Hwang, {William C.} and Sandra Perez and Ge Wei and Daniel Aird and Chen, {Li Mei} and Eugenio Santelli and Boguslaw Stec and Greg Cadwell and Maryam Ali and Hongquan Wan and Akikazu Murakami and Anuradha Yammanuru and Thomas Han and Cox, {Nancy J.} and Bankston, {Laurie A.} and Donis, {Ruben O.} and Liddington, {Robert C.} and Marasco, {Wayne A.}",
note = "Funding Information: We thank J. Appleton (Cornell University) for the gift of mouse mAbs against H5N1, 17A2.1.2 and 22F; A. Klimov (CDC) and A. Balish (CDC) for providing ferret antiserum and virus sequences; R. Webster (St. Jude Children{\textquoteright}s Research Hospital) for H11N9, H13N6 and H16N3; L. Quynh Mai (National Institute of Hygiene and Epidemiology, Vietnam Ministry of Health) for H5N1; W. Lim (Hong Kong Department of Health) for H5N1 and H9N2, as well as E. Sedyaningsih, T. Soendoro (National Institute of Health Research and Development, Indonesian Ministry of Health) for H5N1 specimens; P. Palese (Mount Sinai School of Medicine) for pCAGGS-H1(SC) plasmid encoding the full-length hemagglutinin protein of H1-SC1918; M. Farzan (New England Primate Research Center, Harvard Medical School) for pCAGGS-H1 (PR) plasmid encoding the hemagglutinin protein of H1-PR34 and X. Yang (Beth Israel Deaconess Medical Center, Harvard Medical School) for pCAGGS-H7 (FPV) encoding H7-FP34 hemagglutinin; and R. Fuller (University of Michigan) for furin cDNA. We thank W. Yuan and W. Li for helpful discussions and Y. Lin for assistance in crystallization and critical discussion. We thank the US National Institutes of Health (NIH) and the Department of Energy (DOE) for access to the Stanford Synchrotron Radiation Facility and the facility staff for assistance in X-ray data collection. Molecular graphics images were produced using the UCSF Chimera package from the Resource for Biocomputing, Visualization, and Informatics at the University of California, San Francisco (supported by NIH P41 RR-01081). This work was supported by NIH (U01-AI074518-01) to W.A.M. and in part by NIH (P01-AI055789) to R.C.L.",
year = "2009",
month = mar,
doi = "10.1038/nsmb.1566",
language = "English (US)",
volume = "16",
pages = "265--273",
journal = "Nature Structural Biology",
issn = "1545-9993",
publisher = "Nature Publishing Group",
number = "3",
}