PMID- 26038805 OWN - NLM STAT- MEDLINE DCOM- 20160419 LR - 20181113 IS - 2164-554X (Electronic) IS - 2164-5515 (Print) IS - 2164-5515 (Linking) VI - 11 IP - 7 DP - 2015 TI - Strong protection against ricin challenge induced by a novel modified ricin A-chain protein in mouse model. PG - 1779-87 LID - 10.1080/21645515.2015.1038446 [doi] AB - Ricin toxin (RT) is an extremely potent toxin derived from the castor bean plant. As a possible bioterrorist weapon, it was categorized as a level B agent in international society. With the growing awareness and concerns of the "white powder incident" in recent years, it is indispensable to develop an effective countermeasure against RT intoxication. In this study we used site-directed mutagenesis and polymerase chain reaction (PCR) techniques to modify the gene of ricin A-chain (RTA). As a result, we have generated a mutated and truncated ricin A-chain (mtRTA) vaccine antigen by E.coli strain. The cytotoxicity assay was used to evaluate the safety of the as-prepared mtRTA antigen, and the results showed that there was no residual toxicity observed when compared to the recombinant RTA (rRTA) or native RT. Furthermore, BALB/c mice were subcutaneously (s.c.) vaccinated with mtRTA 3 times at an interval of 2 weeks, and then the survivals were evaluated after intraperitoneal (i.p.) or intratracheal challenge of RT. The vaccinated mice developed a strong protective immune response that was wholly protective against 40 x LD50 of RT i.p. injection or 20 x LD50 of RT intratracheal spraying. The mtRTA antigen has great potential to be a vaccine candidate for future application in humans. FAU - Zhang, Tao AU - Zhang T AD - a State Key Laboratory of Pathogen and Biosecurity; Beijing Institute of Microbiology and Epidemiology ; Beijing , China. FAU - Yang, Hao AU - Yang H FAU - Kang, Lin AU - Kang L FAU - Gao, Shan AU - Gao S FAU - Xin, Wenwen AU - Xin W FAU - Yao, Wenwu AU - Yao W FAU - Zhuang, Xiangjin AU - Zhuang X FAU - Ji, Bin AU - Ji B FAU - Wang, Jinglin AU - Wang J LA - eng PT - Journal Article PL - United States TA - Hum Vaccin Immunother JT - Human vaccines & immunotherapeutics JID - 101572652 RN - 0 (Vaccines) RN - 9009-86-3 (Ricin) SB - IM MH - Administration, Inhalation MH - Animals MH - Bioterrorism MH - Escherichia coli/genetics/metabolism MH - Immunization, Passive MH - Injections, Subcutaneous MH - Lethal Dose 50 MH - Mice MH - Mice, Inbred BALB C MH - Mutagenesis, Site-Directed MH - Neutralization Tests MH - Plasmids/genetics MH - Polymerase Chain Reaction MH - Ricin/administration & dosage/*immunology/*poisoning MH - Survival Analysis MH - Vaccines/administration & dosage/*genetics/*immunology PMC - PMC4514271 OTO - NOTNLM OT - ELISA, enzyme-linked immunosorbent assay OT - FBS, fetal bovine serum OT - HRP, horseradish peroxidase OT - IPTG, isopropyl-1-thio-beta-galactopyranoside OT - LD50, median lethal dose OT - RT, ricin toxin OT - RTA, ricin toxin A chain OT - RTB, ricin toxin B chain OT - SD, standard deviation OT - i.p, intraperitoneally OT - i.p., intraperitoneal OT - immunity OT - intratracheal OT - mRTA, mutated RTA OT - mtRTA, mutated and truncated RTA OT - mutant OT - rRTA, recombinant RTA OT - ricin OT - s.c., subcutaneously subcutaneous OT - toxicity OT - toxin OT - truncation OT - vaccine EDAT- 2015/06/04 06:00 MHDA- 2016/04/20 06:00 PMCR- 2016/02/03 CRDT- 2015/06/04 06:00 PHST- 2015/06/04 06:00 [entrez] PHST- 2015/06/04 06:00 [pubmed] PHST- 2016/04/20 06:00 [medline] PHST- 2016/02/03 00:00 [pmc-release] AID - 1038446 [pii] AID - 10.1080/21645515.2015.1038446 [doi] PST - ppublish SO - Hum Vaccin Immunother. 2015;11(7):1779-87. doi: 10.1080/21645515.2015.1038446.