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

被引:1
|
作者
Peng, Jingyi [1 ,2 ]
Wu, Jiaguo [2 ,3 ]
Shi, Ning [2 ,4 ]
Xu, Hua [2 ]
Luo, Longlong [2 ]
Wang, Jing [2 ]
Li, Xinying [2 ]
Xiao, He [2 ]
Feng, Jiannan [2 ]
Li, Xia [1 ]
Chai, Lihui [1 ]
Qiao, Chunxia [2 ,5 ]
机构
[1] Henan Univ, Affiliated Hosp 1, Sch Med, Joint Natl Lab Antibody Drug Engn, Kaifeng, Peoples R China
[2] Acad Mil Med Sci, Acad Mil Med Sci, Inst Pharmacol & Toxicol, State key Lab Toxicol & Med Countermeasures, Beijing, Peoples R China
[3] Dali Univ, Sch Basic Med Sci, Dept Anat, Dalian, Peoples R China
[4] Cent South Univ, Sch Basic Med Sci, Canc Res Inst, Changsha, Peoples R China
[5] Henan Univ, Sch Pharm, Kaifeng, Peoples R China
来源
FRONTIERS IN IMMUNOLOGY | 2022年 / 13卷
关键词
abrin; humanization; neutralizing antibody; protective effect; computer-aided design; RIBOSOME-INACTIVATING PROTEINS; MONOCLONAL-ANTIBODY; ESCHERICHIA-COLI; RICIN; PROTECTION; TOXIN;
D O I
10.3389/fimmu.2022.831536
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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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页数:10
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