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A Novel Humanized Anti-Abrin A Chain Antibody Inhibits Abrin Toxicity In Vitro and In Vivo

Abrin, a type-II ribosome inactivating protein from the seed of Abrus precatorius, is classified as a Category B bioterrorism warfare agent. Due to its high toxicity, ingestion by animals or humans will lead to death from multiple organ failure. Currently, no effective agents have been reported to t...

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Autores principales: Peng, Jingyi, Wu, Jiaguo, Shi, Ning, Xu, Hua, Luo, Longlong, Wang, Jing, Li, Xinying, Xiao, He, Feng, Jiannan, Li, Xia, Chai, Lihui, Qiao, Chunxia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8855095/
https://www.ncbi.nlm.nih.gov/pubmed/35185923
http://dx.doi.org/10.3389/fimmu.2022.831536
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author Peng, Jingyi
Wu, Jiaguo
Shi, Ning
Xu, Hua
Luo, Longlong
Wang, Jing
Li, Xinying
Xiao, He
Feng, Jiannan
Li, Xia
Chai, Lihui
Qiao, Chunxia
author_facet Peng, Jingyi
Wu, Jiaguo
Shi, Ning
Xu, Hua
Luo, Longlong
Wang, Jing
Li, Xinying
Xiao, He
Feng, Jiannan
Li, Xia
Chai, Lihui
Qiao, Chunxia
author_sort Peng, Jingyi
collection PubMed
description Abrin, a type-II ribosome inactivating protein from the seed of Abrus precatorius, is classified as a Category B bioterrorism warfare agent. Due to its high toxicity, ingestion by animals or humans will lead to death from multiple organ failure. Currently, no effective agents have been reported to treat abrin poisoning. In this study, a novel anti-abrin neutralizing antibody (S008) was humanized using computer-aided design, which possessed lower immunogenicity. Similar to the parent antibody, a mouse anti-abrin monoclonal antibody, S008 possessed high affinity and showed a protective effect against abrin both in vitro and in vivo, and protected mice that S008 was administered 6 hours after abrin. S008 was found that it did not inhibit entry of abrin into cells, suggesting an intracellular blockade capacity against the toxin. In conclusion, this work demonstrates that S008 is a high affinity anti-abrin antibody with both a neutralizing and protective effect and may be an excellent candidate for clinical treatment of abrin poisoning.
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spelling pubmed-88550952022-02-19 A Novel Humanized Anti-Abrin A Chain Antibody Inhibits Abrin Toxicity In Vitro and In Vivo Peng, Jingyi Wu, Jiaguo Shi, Ning Xu, Hua Luo, Longlong Wang, Jing Li, Xinying Xiao, He Feng, Jiannan Li, Xia Chai, Lihui Qiao, Chunxia Front Immunol Immunology Abrin, a type-II ribosome inactivating protein from the seed of Abrus precatorius, is classified as a Category B bioterrorism warfare agent. Due to its high toxicity, ingestion by animals or humans will lead to death from multiple organ failure. Currently, no effective agents have been reported to treat abrin poisoning. In this study, a novel anti-abrin neutralizing antibody (S008) was humanized using computer-aided design, which possessed lower immunogenicity. Similar to the parent antibody, a mouse anti-abrin monoclonal antibody, S008 possessed high affinity and showed a protective effect against abrin both in vitro and in vivo, and protected mice that S008 was administered 6 hours after abrin. S008 was found that it did not inhibit entry of abrin into cells, suggesting an intracellular blockade capacity against the toxin. In conclusion, this work demonstrates that S008 is a high affinity anti-abrin antibody with both a neutralizing and protective effect and may be an excellent candidate for clinical treatment of abrin poisoning. Frontiers Media S.A. 2022-02-04 /pmc/articles/PMC8855095/ /pubmed/35185923 http://dx.doi.org/10.3389/fimmu.2022.831536 Text en Copyright © 2022 Peng, Wu, Shi, Xu, Luo, Wang, Li, Xiao, Feng, Li, Chai and Qiao https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Peng, Jingyi
Wu, Jiaguo
Shi, Ning
Xu, Hua
Luo, Longlong
Wang, Jing
Li, Xinying
Xiao, He
Feng, Jiannan
Li, Xia
Chai, Lihui
Qiao, Chunxia
A Novel Humanized Anti-Abrin A Chain Antibody Inhibits Abrin Toxicity In Vitro and In Vivo
title A Novel Humanized Anti-Abrin A Chain Antibody Inhibits Abrin Toxicity In Vitro and In Vivo
title_full A Novel Humanized Anti-Abrin A Chain Antibody Inhibits Abrin Toxicity In Vitro and In Vivo
title_fullStr A Novel Humanized Anti-Abrin A Chain Antibody Inhibits Abrin Toxicity In Vitro and In Vivo
title_full_unstemmed A Novel Humanized Anti-Abrin A Chain Antibody Inhibits Abrin Toxicity In Vitro and In Vivo
title_short A Novel Humanized Anti-Abrin A Chain Antibody Inhibits Abrin Toxicity In Vitro and In Vivo
title_sort novel humanized anti-abrin a chain antibody inhibits abrin toxicity in vitro and in vivo
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8855095/
https://www.ncbi.nlm.nih.gov/pubmed/35185923
http://dx.doi.org/10.3389/fimmu.2022.831536
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