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A chimeric protein of abrin and Abrus precatorius agglutinin that neutralizes abrin mediated lethality in mice

Tiwari, Vinita, Bagaria, Shradha, Karande, Anjali A.
Toxicon 2017
Abrus precatorius, agglutinins, amino acids, clinical trials, epitopes, immunization, lethal dose 50, mice, neutralization, neutralizing antibodies, poisoning, recombinant fusion proteins, ricin, vaccines
Abrin, a type II ribosome inactivating protein from the Abrus precatorius plant, is extremely toxic. It has been shown to be 75 times more potent than its infamous sister toxin, ricin and their potential use in bio-warfare is a cause of major concern. Although several vaccine candidates are under clinical trials for ricin, none are available against abrin. The present study proposes a chimeric protein, comprising of 1–123 amino acids taken from the A chain of abrin and 124–175 amino acids from Abrus precatorius agglutinin A chain, as a vaccine candidate against abrin intoxication. The design was based on the inclusion of the immunogenic region of the full length protein and the minimal essential folding domains required for inducing neutralizing antibody response. The chimera also contains the epitope for the only two neutralizing antibodies; D6F10 and A7C4, reported against abrin till now. Active immunisation with the chimera protected all the mice challenged with 45 X LD50 of abrin. Also, passive transfer of antibodies raised against the chimera rescued all mice challenged with 50 X LD50 of toxin. Hence the chimeric protein appears to be a promising vaccine candidate against abrin induced lethality.