1. Biophysics and Structural Biology
  2. Microbiology and Infectious Disease
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Extended low-resolution structure of a Leptospira antigen offers high bactericidal antibody accessibility amenable to vaccine design

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Cite as: eLife 2017;6:e30051 doi: 10.7554/eLife.30051

Abstract

Pathogens rely on proteins embedded on their surface to perform tasks essential for host infection. These obligatory structures exposed to the host immune system provide important targets for rational vaccine design. Here, we use a systematically designed series of multi-domain constructs in combination with small angle X-ray scattering (SAXS) to determine the structure of the main immunoreactive region from a major antigen from Leptospira interrogans, LigB. An anti-LigB monoclonal antibody library exhibits cell binding and bactericidal activity with extensive domain coverage complementing the elongated architecture observed in the SAXS structure. Combining antigenic motifs in a single-domain chimeric immunoglobulin-like fold generated a vaccine that greatly enhances leptospiral protection over vaccination with single parent domains. Our study demonstrates how understanding an antigen's structure and antibody accessible surfaces can guide the design and engineering of improved recombinant antigen-based vaccines.

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Author details

  1. Ching-Lin Hsieh

    Department of Population Medicine and Diagnostic Sciences, Cornell University, Ithaca, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Christopher P Ptak

    Department of Population Medicine and Diagnostic Sciences, Cornell University, Ithaca, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon 0000-0003-2752-0367
  3. Andrew Tseng

    Department of Population Medicine and Diagnostic Sciences, Cornell University, Ithaca, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Igor Massahiro de Souza Suguiura

    Department of Population Medicine and Diagnostic Sciences, Cornell University, Ithaca, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Sean P McDonough

    Department of Biomedical Sciences, Cornell University, Ithaca, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Tepyuda Sritrakul

    Department of Population Medicine and Diagnostic Sciences, Cornell University, Ithaca, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Ting Li

    Department of Population Medicine and Diagnostic Sciences, Cornell University, Ithaca, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Yi-Pin Lin

    Division of Infectious Disease, New York State Department of Health, Albany, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Richard E Gillilan

    Cornell High Energy Synchrotron Source, Cornell University, Ithaca, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon 0000-0002-7636-3188
  10. Robert Oswald

    Department of Molecular Medicine, Cornell University, Ithaca, United States
    For correspondence
    reo1@cornell.edu
    Competing interests
    The authors declare that no competing interests exist.
  11. Yung-Fu Chang

    Department of Population Medicine and Diagnostic Sciences, Cornell University, Ithaca, United States
    For correspondence
    yc42@cornell.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon 0000-0001-8902-3089

Funding

Center for Advanced Technology program (478-3400)

  • Yung-Fu Chang

Biotechnology Research and Development Corporation (478-9355)

  • Yung-Fu Chang

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: Animals were housed in isolation units approved by the Cornell University Institutional Animal Care and Use Committee (Protocol number: 2015-0133).

Reviewing Editor

  1. Volker Dötsch, Reviewing Editor, J.W. Goethe-University, Germany

Publication history

  1. Received: June 29, 2017
  2. Accepted: December 2, 2017
  3. Accepted Manuscript published: December 6, 2017 (version 1)

Copyright

© 2017, Hsieh et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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