High-throughput immuno-profiling of mamba (Dendroaspis) venom toxin epitopes using high-density peptide microarrays

Mikael Engmark, Mikael Rørdam Andersen, Andreas Hougaard Laustsen, Jigar Patel, Eric Sullivan, Federico De Masi, Christian Skjødt Hansen, Jens Vindahl Kringelum, Bruno Lomonte, José María Gutiérrez, Ole Lund

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    Abstract

    Snakebite envenoming is a serious condition requiring medical attention and administration of antivenom. Current antivenoms are antibody preparations obtained from the plasma of animals immunised with whole venom(s) and contain antibodies against snake venom toxins, but also against other antigens. In order to better understand the molecular interactions between antivenom antibodies and epitopes on snake venom toxins, a high-throughput immuno-profiling study on all manually curated toxins from Dendroaspis species and selected African Naja species was performed based on custom-made high-density peptide microarrays displaying linear toxin fragments. By detection of binding for three different antivenoms and performing an alanine scan, linear elements of epitopes and the positions important for binding were identified. A strong tendency of antivenom antibodies recognizing and binding to epitopes at the functional sites of toxins was observed. With these results, high-density peptide microarray technology is for the first time introduced in the field of toxinology and molecular details of the evolution of antibody-toxin interactions based on molecular recognition of distinctive toxic motifs are elucidated.
    Original languageEnglish
    Article number36629
    JournalScientific Reports
    Volume6
    Number of pages14
    ISSN2045-2322
    DOIs
    Publication statusPublished - 2016

    Bibliographical note

    This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

    Keywords

    • Antibody therapy
    • High-throughput screening
    • Immunization
    • Molecular evolution
    • Molecular medicine

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