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Vaccine. 2015 Jul 31;33(32):3836-42. doi: 10.1016/j.vaccine.2015.06.096. Epub 2015 Jun 30.

Monoclonal antibody, mAb 4C13, an effective detoxicant antibody against ricin poisoning.

Author information

1
Beijing Institute of Pharmacology and Toxicology, State Key Laboratory of Toxicology and Medical Countermeasures, Beijing 100850, China.
2
Beijing Institute of Basic Medical Sciences, Beijing 100850, China.
3
Beijing Institute of Pharmacology and Toxicology, State Key Laboratory of Toxicology and Medical Countermeasures, Beijing 100850, China; Beijing Institute of Basic Medical Sciences, Beijing 100850, China.
4
Beijing Institute of Pharmacology and Toxicology, State Key Laboratory of Toxicology and Medical Countermeasures, Beijing 100850, China. Electronic address: wangyuxia1962@hotmail.com.
5
Beijing Institute of Basic Medical Sciences, Beijing 100850, China. Electronic address: fengjiannan1970@aliyun.com.

Abstract

Ricin is a glycoprotein produced in castor seeds and consists of two polypeptide chains named Ricin Toxin A Chain (RTA) and Ricin Toxin B Chain (RTB), linked via a disulfide bridge. Due to its high toxicity, ricin is regarded as a high terrorist risk for the public. However, antibodies can play a pivotal role in neutralizing the toxin. In this research, the anti-toxicant effect of mAb 4C13, a monoclonal antibody (mAb) established using detoxicated ricin as the immunized antigen, was evaluated. Compared with mAb 4F2 and mAb 5G6, the effective mechanism of mAb 4C13 was analyzed by experiments relating to its cytotoxicity, epitope on ricin, binding kinetics with the toxin, its blockage on the protein synthesis inhibition induced by ricin and the intracelluar tracing of its complex with ricin. Our result indicated that mAb 4C13 could recognize and bind to RTA, RTB and exert its high affinity to the holotoxin. Both cytotoxicity and animal toxicity of ricin were well blocked by pre-incubating the toxin with mAb 4C13. By intravenous injection, mAb 4C13 could rescue the mouse intraperitoneally (ip) injected with a lethal dose of ricin (20μg/kg) even at 6h after the intoxication and its efficacy was dependent on its dosage. This research indicated that mAb 4C13 could be an excellent candidate for therapeutic antibodies. Its potent antitoxic efficiency was related to its recognition on the specific epitope with very high affinity and its blockage of protein synthesis inhibition in cytoplasm followed by cellular internalization with ricin.

KEYWORDS:

Bioterrorism; Monoclonal antibody; Ricin

PMID:
26141013
DOI:
10.1016/j.vaccine.2015.06.096
[Indexed for MEDLINE]

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