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A complex of influenza hemagglutinin with a neutralizing antibody that binds outside the virus receptor binding site

Nature Structural Biology volume 6, pages 530–534 (1999)Cite this article

Abstract

The structure of a complex of influenza hemagglutinin (HA) with a neutralizing antibody shows that the antibody binds to HA at a distance from the virus receptor binding site. Comparison of the properties of this antibody and its Fab with those of an antibody that recognizes an epitope overlapping the receptor binding site leads to two main conclusions. First, inhibition of receptor binding is an important component of neutralization. Second, the efficiency of neutralization by the antibodies ranks in the same order as their avidities for HA, and their large size makes these antibodies highly efficient at neutralization, regardless of the location of their epitope in relation to the virus receptor binding site. These observations provide rationales for the range of antibody specificities that are detected in immune sera and for the distribution of sequence changes on the membrane-distal surface of influenza HAs that occur during 'antigenic drift.'

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Figure 1: The X31 HA–HC45 Fab complex.
Figure 2: Neutralization of X31 influenza virus.

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Acknowledgements

We thank the staff of the LURE and ESRF for their help during data collection, and A. Douglas, B. Gigant, R. Gonsalves and D. Stevens for excellent assistance. This work was supported by a grant from the EU BIOMED program.

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Author notes

  1. Damien Fleury

    Present address: L.C.M.,I.B.S., 41, rue Jules Horowitz, 38027 Cedex 1, Grenoble, France

  2. Damien Fleury and Béatrice Barrère: These authors contributed equally to this work.

Authors and Affiliations

  1. Laboratoire d'Enzymologie et Biochimie Structurales, UPR 9063, CNRS, Bât. 34, CNRS, Gif-sur-Yvette, 91198, Cedex, France

    Damien Fleury, Thierry Bizebard & Marcel Knossow

  2. National Institute for Medical Research, Mill Hill, NW7 1AA, London, UK

    Béatrice Barrère, Rod S. Daniels & John J. Skehel

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Fleury, D., Barrère, B., Bizebard, T. et al. A complex of influenza hemagglutinin with a neutralizing antibody that binds outside the virus receptor binding site . Nat Struct Mol Biol 6, 530–534 (1999). https://doi.org/10.1038/9299

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