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.