Article abstract
Nature Structural & Molecular Biology 16, 265 - 273 (2009)
Published online: 22 February 2009 | doi:10.1038/nsmb.1566
Structural and functional bases for broad-spectrum neutralization of avian and human influenza A viruses
Jianhua Sui1,4, William C Hwang2,4, Sandra Perez3, Ge Wei2, Daniel Aird1, Li-mei Chen3, Eugenio Santelli2, Boguslaw Stec2, Greg Cadwell2, Maryam Ali1, Hongquan Wan3, Akikazu Murakami1, Anuradha Yammanuru1, Thomas Han1, Nancy J Cox3, Laurie A Bankston2, Ruben O Donis3, Robert C Liddington2 & Wayne A Marasco1
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.
- Department of Cancer Immunology & AIDS, Dana-Farber Cancer Institute; Department of Medicine, Harvard Medical School, 44 Binney Street JFB 826, Boston, Massachusetts 02115, USA.
- Infectious and Inflammatory Disease Center, Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, California 92037, USA.
- Influenza Division, Centers for Disease Control and Prevention, National Center for Immunization and Respiratory Diseases, 1600 Clifton Road, Mail Stop G-16, Atlanta, Georgia 30333, USA.
- These authors contributed equally to this work.
Correspondence to: Jianhua Sui1,4 e-mail: jianhua_sui@dfci.harvard.edu
Correspondence to: Ruben O Donis3 e-mail: rvd6@cdc.gov
Correspondence to: Robert C Liddington2 e-mail: rlidding@burnham.org
Correspondence to: Wayne A Marasco1 e-mail: wayne_marasco@dfci.harvard.edu
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