Abstract
Abrin toxin is a type 2 ribosome inactivating glycoprotein isolated from the seeds of Abrus precatorius (jequirity pea). Owing to its high toxicity, relative ease of purification and accessibility, it is considered a biological threat agent. To date, there is no effective post-exposure treatment for abrin poisoning and passive immunization remains the most effective therapy. However, the effectiveness of anti-abrin monoclonal antibodies for post-exposure therapy following abrin intoxication has not been demonstrated. The aim of this study was to isolate high affinity anti-abrin antibodies that possess potent toxin-neutralization capabilities. An immune scFv phage-display library was constructed from an abrin-immunized rabbit and a panel of antibodies (six directed against the A subunit of abrin and four against the B subunit) was isolated and expressed as scFv-Fc antibodies. By pair-wise analysis, we found that these antibodies target five distinct epitopes on the surface of abrin and that antibodies against all these sites can bind the toxin simultaneously. Several of these antibodies (namely, RB9, RB10, RB28 and RB30) conferred high protection against pulmonary intoxication of mice, when administered six hours post exposure to a lethal dose of abrin. The data presented in this study demonstrate for the first time the efficacy of monoclonal antibodies in treatment of mice after pulmonary intoxication with abrin and promote the use of these antibodies, one or several, for post-exposure treatment of abrin intoxication.
Highlights
Abrin toxin is a 66 kDa type 2 ribosome inactivating glycoprotein (RIP), isolated from the seeds ofAbrus precatorius
The immunization strategy consisted of initial priming of the rabbit with sub-lethal quantities of alum-adhered abrin followed by additional boost injections consisting of high amounts of toxin, mixed with incomplete
Over time, a sharp increase in antibody titers was measured with a concomitant increase in their ability to neutralize abrin (Figure 1)
Summary
Abrin toxin is a 66 kDa type 2 ribosome inactivating glycoprotein (RIP), isolated from the seeds of. Several anti-abrin monoclonal antibodies (mABs) were isolated, several targeting ATA and only one targeting ATB. We have previously isolated a panel of potent anti-ricin mABs [12] by incorporating immunization methodologies that promote high affinity antibodies in vivo, together with efficient screening methods using phage-display libraries. These antibodies were shown to confer an extended therapeutic window for post-exposure treatment of mice that were exposed to pulmonary intoxication of ricin [13]. We report the immunization strategy and antibody selection procedures taken to reach this end and describe the set of novel anti-abrin antibodies identified
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