Truncated abrin A chain expressed inEscherichia 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.

Surface display of PbrR on Escherichia coli and evaluation of the bioavailability of lead associated with engineered cells in mice

“…In order to determine the effect of oral administration of PbrR-displayed E . coli on mice, we subsequently performed a short-term in vivo toxicity assays using recombinant bacteria 39 , 40 . No morbidities or mortalities were observed during the experiment as shown in Table 1 .…”

“…In vivo toxicity assay of recombinant bacteria was done as described previously 39 , 40 . Male Kunming (KM) mice, 4~5 weeks old and weighing 18~22 g, obtained from Guangdong Medical Laboratory Animal Center, were used for in vivo toxicity assay.…”

A novel recombinant vaccine protecting mice against abrin intoxication

“…To date, vaccine researches against toxins of A-B family, including AT and RT, have focused on toxoid and A chain subunit, especially the latter. For instance, deglycosylated RTA (dgRTA), 8 7 are all based on A chain. As for AT vaccine, ATA mutant could provide the complete protection against challenge at a dose 10 times higher than the LD 50 of AT.…”

“…2,6 Both procedures are effective in the prophylaxis or therapy of toxin poisoning in mice. Currently, only vaccines based on a toxoid of AT ( attenuated with formalin as reported by Griffiths 5 ) and A chain subunit ( ATA mutant 1 and truncated ATA 7 ) produced in our lab, were effective in neutralizing intoxication by AT. This toxoid was effective in preventing death by intoxication.…”

A Novel Humanized Anti-Abrin A Chain Antibody Inhibits Abrin Toxicity In Vitro and In Vivo

“…In mice, generation of protective antibodies can be induced with a sub-lethal dose of abrin (10,11). Recombinant abrin A chain (12)(13)(14)(15) or the weaker abrin B chain (16)(17)(18)(19), can also induce anti-abrin antibody production. Up to now, only two neutralizing antibodies against Abrin poisoning have been reported, D6F10 and A7C4, but neither has entered clinical trials or been used directly in humans.…”