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Toxins 2018, 10(2), 80; https://doi.org/10.3390/toxins10020080

Novel Phage Display-Derived Anti-Abrin Antibodies Confer Post-Exposure Protection against Abrin Intoxication

1
Department of Infectious Diseases, Israel Institute for Biological Research, Ness-Ziona 76100, Israel
2
Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona 76100, Israel
3
Department of Biotechnology, Israel Institute for Biological Research, Ness-Ziona 76100, Israel
*
Author to whom correspondence should be addressed.
Received: 15 January 2018 / Revised: 6 February 2018 / Accepted: 8 February 2018 / Published: 13 February 2018
(This article belongs to the Section Plant Toxins)
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Abstract

Abrin toxin is a type 2 ribosome inactivating glycoprotein isolated from the seeds of Abrus precatorius (jequirity pea). Owing to its high toxicity, relative ease of purification and accessibility, it is considered a biological threat agent. To date, there is no effective post-exposure treatment for abrin poisoning and passive immunization remains the most effective therapy. However, the effectiveness of anti-abrin monoclonal antibodies for post-exposure therapy following abrin intoxication has not been demonstrated. The aim of this study was to isolate high affinity anti-abrin antibodies that possess potent toxin-neutralization capabilities. An immune scFv phage-display library was constructed from an abrin-immunized rabbit and a panel of antibodies (six directed against the A subunit of abrin and four against the B subunit) was isolated and expressed as scFv-Fc antibodies. By pair-wise analysis, we found that these antibodies target five distinct epitopes on the surface of abrin and that antibodies against all these sites can bind the toxin simultaneously. Several of these antibodies (namely, RB9, RB10, RB28 and RB30) conferred high protection against pulmonary intoxication of mice, when administered six hours post exposure to a lethal dose of abrin. The data presented in this study demonstrate for the first time the efficacy of monoclonal antibodies in treatment of mice after pulmonary intoxication with abrin and promote the use of these antibodies, one or several, for post-exposure treatment of abrin intoxication. View Full-Text
Keywords: abrin; monoclonal antibodies; phage-display; rabbit; recombinant antibodies abrin; monoclonal antibodies; phage-display; rabbit; recombinant antibodies
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Mechaly, A.; Alcalay, R.; Noy-Porat, T.; Epstein, E.; Gal, Y.; Mazor, O. Novel Phage Display-Derived Anti-Abrin Antibodies Confer Post-Exposure Protection against Abrin Intoxication. Toxins 2018, 10, 80.

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