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Influenza Pathogenesis and Control - Volume II pp 323–341Cite as

Structural Characterization of Viral Epitopes Recognized by Broadly Cross-Reactive Antibodies

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Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 386))

Abstract

Influenza hemagglutinin (HA) is the major surface glycoprotein on influenza viruses and mediates viral attachment and subsequent fusion with host cells. The HA is the major target of the immune response, but due to its high level of variability, as evidenced by substantial antigenic diversity, it had been historically considered to elicit only a narrow, strain-specific antibody response. However, a recent explosion in the discovery of broadly neutralizing antibodies (bnAbs) to influenza virus has identified two major supersites of vulnerability on the HA through structural characterization of HA-antibody complexes. These commonly targeted epitopes are involved with receptor binding as well as the fusion machinery and, hence, are functionally conserved and less prone to mutation. These bnAbs can neutralize viruses by blocking infection or the spread of infection by preventing progeny release. Structural analyses of these bnAbs show they exhibit striking similarities and trends in recognition of the HA and use recurring recognition motifs, despite substantial differences in their germline genes. This information can be utilized in design of novel therapeutics as well as in immunogens for improved vaccines with greater breadth and efficacy.

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Abbreviations

bnAb:

Broadly neutralizing antibody

CDR:

Complementarity determining region

EM:

Electron microscopy

Fab:

Fragment antigen binding

HA:

Hemagglutinin

IgG:

Immunoglobulin G

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Authors and Affiliations

  1. Department of Integrative Structural and Computational Biology and Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, USA

    Peter S. Lee & Ian A. Wilson

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  1. Peter S. Lee
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  2. Ian A. Wilson
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Correspondence to Ian A. Wilson .

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Editors and Affiliations

  1. Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California, USA

    Michael B. A. Oldstone

  2. IDepartment of Microbiology and Immunology, Emory University, Atlanta, Georgia, USA

    Richard W. Compans

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Lee, P.S., Wilson, I.A. (2014). Structural Characterization of Viral Epitopes Recognized by Broadly Cross-Reactive Antibodies. In: Oldstone, M., Compans, R. (eds) Influenza Pathogenesis and Control - Volume II. Current Topics in Microbiology and Immunology, vol 386. Springer, Cham. https://doi.org/10.1007/82_2014_413

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