Neutralizing Monoclonal Antibody, mAb 10D8, Is an Effective Detoxicant against Abrin-a Both In Vitro and In Vivo
Zhi Li,
Hua Xu,
Bo Ma,
Li Luo,
Lei Guo,
Pingping Zhang,
Yong Zhao,
Lili Wang,
Jianwei Xie
Affiliations
Zhi Li
State Key Laboratory of Toxicology and Medical Countermeasures, Laboratory of Toxicant Analysis, Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing 100850, China
Hua Xu
State Key Laboratory of Toxicology and Medical Countermeasures, Laboratory of Toxicant Analysis, Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing 100850, China
Bo Ma
State Key Laboratory of Toxicology and Medical Countermeasures, Laboratory of Toxicant Analysis, Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing 100850, China
Li Luo
State Key Laboratory of Toxicology and Medical Countermeasures, Laboratory of Toxicant Analysis, Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing 100850, China
Lei Guo
State Key Laboratory of Toxicology and Medical Countermeasures, Laboratory of Toxicant Analysis, Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing 100850, China
Pingping Zhang
State Key Laboratory of Pathogen and Biosecurity, Beijing Key Laboratory of POCT for Bioemergency and Clinic, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China
Yong Zhao
State Key Laboratory of Pathogen and Biosecurity, Beijing Key Laboratory of POCT for Bioemergency and Clinic, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, China
Lili Wang
State Key Laboratory of Toxicology and Medical Countermeasures, Laboratory of Toxicant Analysis, Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing 100850, China
Jianwei Xie
State Key Laboratory of Toxicology and Medical Countermeasures, Laboratory of Toxicant Analysis, Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing 100850, China
Abrin is a types II ribosome-inactivating protein (RIP) isolated from Abrus precatorious seeds, which comprises a catalytically active A chain and a lectin-like B chain linked by a disulfide bond. Four isotoxins of abrin have been reported with similar amino-acid composition but different cytotoxicity, of which abrin-a is the most potent toxin. High lethality and easy availability make abrin a potential bioterrorism agent. However, there are no antidotes available for managing abrin poisoning, and treatment is only symptomatic. Currently, neutralizing antibodies remain the most effective therapy against biotoxin poisoning. In this study, we prepared, identified, and acquired a high-affinity neutralizing monoclonal antibody (mAb) 10D8 with a potent pre- and post-exposure protective effect against cytotoxicity and animal toxicity induced by abrin-a or abrin crude extract. The mAb 10D8 could rescue the mouse injected intraperitoneally with a 25 × LD50 dose of abrin-a from lethality and prevent tissue damages. Results indicated that 10D8 does not prevent the binding and internalization of abrin-a to cells but inhibits the enzymatic activity of abrin-a and reduces protein synthesis inhibition of cells. The high affinity, good specificity, and potent antitoxic efficiency of 10D8 make it a promising candidate for therapeutic antibodies against abrin.
