title: Monoclonal antibody, mAb 4C13, an effective detoxicant antibody against ricin poisoning.
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.
authors.affiliation: Beijing Institute of Pharmacology and Toxicology, State Key Laboratory of Toxicology and Medical Countermeasures, Beijing 100850, China.
authors.forename: Na
authors.initials: N
authors.lastname: Dong
authors.affiliation: Beijing Institute of Basic Medical Sciences, Beijing 100850, China.
authors.forename: Longlong
authors.initials: L
authors.lastname: Luo
authors.affiliation: Beijing Institute of Pharmacology and Toxicology, State Key Laboratory of Toxicology and Medical Countermeasures, Beijing 100850, China.
authors.forename: Junhua
authors.initials: J
authors.lastname: Wu
authors.affiliation: Beijing Institute of Pharmacology and Toxicology, State Key Laboratory of Toxicology and Medical Countermeasures, Beijing 100850, China.
authors.forename: Peiyuan
authors.initials: P
authors.lastname: Jia
authors.affiliation: 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.
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.affiliation: Beijing Institute of Pharmacology and Toxicology, State Key Laboratory of Toxicology and Medical Countermeasures, Beijing 100850, China. Electronic address: wangyuxia1962@hotmail.com.
authors.forename: Yuxia
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Beijing Institute of Pharmacology and Toxicology, State Key Laboratory of Toxicology and Medical Countermeasures, Beijing 100850, China.
authors.forename: Zhongcai
authors.initials: Z
authors.lastname: Gao
authors.affiliation: Beijing Institute of Basic Medical Sciences, Beijing 100850, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Peng
authors.affiliation: Beijing Institute of Basic Medical Sciences, Beijing 100850, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Lv
authors.affiliation: Beijing Institute of Pharmacology and Toxicology, State Key Laboratory of Toxicology and Medical Countermeasures, Beijing 100850, China.
authors.forename: Chunqian
authors.initials: C
authors.lastname: Huang
authors.affiliation: Beijing Institute of Basic Medical Sciences, Beijing 100850, China. Electronic address: fengjiannan1970@aliyun.com.
authors.forename: Jiannan
authors.initials: J
authors.lastname: Feng
authors.affiliation: Beijing Institute of Pharmacology and Toxicology, State Key Laboratory of Toxicology and Medical Countermeasures, Beijing 100850, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Li
authors.affiliation: Beijing Institute of Pharmacology and Toxicology, State Key Laboratory of Toxicology and Medical Countermeasures, Beijing 100850, China.
authors.forename: Junjie
authors.initials: J
authors.lastname: Shan
authors.affiliation: Beijing Institute of Pharmacology and Toxicology, State Key Laboratory of Toxicology and Medical Countermeasures, Beijing 100850, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Han
authors.affiliation: Beijing Institute of Basic Medical Sciences, Beijing 100850, China.
authors.forename: Beifen
authors.initials: B
authors.lastname: Shen
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000302:isolation & purification / Q000627:therapeutic use*; D000992:Antitoxins / Q000302:isolation & purification / Q000627:therapeutic use*; D004195:Disease Models, Animal; D008807:Mice, Inbred BALB C; D011041:Poisoning / Q000628:therapy*; D012276:Ricin / Q000037:antagonists & inhibitors*; D016019:Survival Analysis
chemical_list: D000911:Antibodies, Monoclonal; D000992:Antitoxins; D012276:Ricin
keywords: Bioterrorism; Monoclonal antibody; Ricin