title: Truncated abrin A chain expressed in Escherichia coli: a promising vaccine candidate.
abstract: Abrin toxin (AT) is a highly potent toxin, and is classified as one of the most important biological warfare and bioterrorism agents. There is currently no approved vaccine for AT. Therefore, the development of an effective vaccine is important in the prevention of intoxication by abrin. In this study, five vectors containing different gene of truncated abrin toxin A chain (tATA) fragments were constructed, and two of them (tATA1(1-126), tATA4(1-188)) were successfully expressed as a soluble form in E.coli strain. Both of the two tATA retained most of their immunogenicity with either low or no toxic effects as determined by both in vitro and in vivo assays. They were used to immunize BALB/c mice three times at an interval of three weeks apart. As a result, the tATA1 can elicite 80% protective efficacy against i.p. challenge of 5×LD50 of abrin, and the tATA4 provides a better protection, which can elicite 100% protective efficacy against intraperitoneal challenge of 40×LD50 of abrin. The superior fragment (tATA4(1-188)) should be considered as a promising vaccine candidate for further investigations.
authors.affiliation: a State Key Laboratory of Pathogen and Biosecurity ; The Institute of Microbiology and Epidemiology; Academy of Military Medical Sciences ; Beijing , PR China.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.forename: Lin
authors.initials: L
authors.lastname: Kang
authors.forename: Shan
authors.initials: S
authors.lastname: Gao
authors.forename: Hao
authors.initials: H
authors.lastname: Yang
authors.forename: Wenwen
authors.initials: W
authors.lastname: Xin
authors.forename: Junhong
authors.initials: J
authors.lastname: Wang
authors.forename: Maowen
authors.initials: M
authors.lastname: Guo
authors.forename: Jinglin
authors.initials: J
authors.lastname: Wang
mesh_terms: D000036:Abrin / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology* / Q000633:toxicity; D000818:Animals; D052179:Antigens, Plant / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D000992:Antitoxins / Q000276:immunology*; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D005822:Genetic Vectors; D008807:Mice, Inbred BALB C; D011041:Poisoning / Q000517:prevention & control*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D016019:Survival Analysis; D014611:Vaccination / Q000379:methods; D014612:Vaccines / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification
chemical_list: D052179:Antigens, Plant; D000992:Antitoxins; D011994:Recombinant Proteins; D014612:Vaccines; D000036:Abrin
keywords: AU, absorbance unit; BSA, bovine serum albumin; E.coli, Escherichia coli; IPTG, isopropyl-1-thio-β-galactopyranoside; LD50, 50% lethal dose; PBS, phosphate–buffered saline solution; PCR, polymerase chain reaction; SD, standard deviation; abrin; i.g., intragastric; i.n., intranasal; i.p., intraperitoneal/intraperitoneally; immunity; pAb, polyclonal antibody; protection; rATA, recombinant A chain of abrin toxin; s.c., subcutaneous/subcutaneously; tATA, truncated A chain of abrin toxin; toxicity; toxin; truncated protein; vaccine