Extended low-resolution structure of a Leptospira antigen offers high bactericidal antibody accessibility amenable to vaccine design
- Cornell University, United States
- New York State Department of Health, United States
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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Article and author information
Author details
Christopher P Ptak
Richard E Gillilan
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.
Reviewing Editor
- Volker Dötsch, J.W. Goethe-University, Germany
Ethics
Animal experimentation: Animals were housed in isolation units approved by the Cornell University Institutional Animal Care and Use Committee (Protocol number: 2015-0133).
Version history
- Received: June 29, 2017
- Accepted: December 2, 2017
- Accepted Manuscript published: December 6, 2017 (version 1)
- Version of Record published: January 2, 2018 (version 2)
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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Extended low-resolution structure of a Leptospira antigen offers high bactericidal antibody accessibility amenable to vaccine design
eLife 6:e30051.
https://doi.org/10.7554/eLife.30051
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