Abrin and Immunoneutralization: A Review

Abstract

Abrin is a type II ribosome-inactivating protein obtained from the mature seeds of a subtropical plant named Abrus precatorius. It is a glycoprotein which arrests protein synthesis in eukaryotes by inactivating ribosomes irreversibly. The heterodimeric protein comprises of the toxic subunit, the A chain which is disulfide bonded to the B chain, a galactose-specific lectin, which helps in binding and trafficking of the toxin in cells. A single molecule of the abrin A chain which reaches the cytosol is sufficient to kill the cell. Owing to its extreme toxicity and ease of purification and dissemination, abrin is considered as a dreaded bioterror agent. In spite of several reports on abrin poisoning, there is no effective antidote or vaccine available against the lethal toxin. An active site mutant of the abrin A chain has been proposed as a potential vaccine candidate against abrin intoxication, though it might not be useful for public at large. However, passive administration of antibodies has served as the primary mode of therapy against a large number of toxins. To date, the monoclonal antibody D6F10 is the only known neutralizing antibody reported against abrin. The antibody can rescue cells as well as mice challenged with lethal doses of the toxin. A recent study has demonstrated that the epitope corresponding to the antibody is present in close proximity to the active site of abrin A chain and the antibody can neutralize abrin-mediated cytotoxicity intracellularly. Humanization of the antibody and a detailed understanding of the trafficking of the abrin-antibody complex are required for its development as therapy, pre-and post-abrin exposure.