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A/B toxins, produced by bacteria and plants, are among the deadliest molecules known. The B chain binds the cell, whereas the A chain exerts the toxic effect. Both anti-A chain and anti-B chain Abs can neutralize toxins in vivo and in vitro. B chain Abs block binding of the toxin to the cell. It is not known how anti-A chain Abs function. Working with ricin toxin, we demonstrate that immunization with A chain induces greater protection than immunization with B chain. A panel of mAbs, binding to A chain, B chain, or both chains, has been produced and characterized. Immunologic characteristics evaluated include isotype, relative avidity, and epitope specificity. The ability to inhibit ricin enzymatic or cell binding activity was studied, as was the ability to block ricin-mediated cellular cytotoxicity on human and murine cell lines. Finally, the in vivo protective efficacy of the Abs in mice was studied. The Ab providing the greatest in vivo protective efficacy was directed against the A chain. It had the greatest relative avidity and the greatest ability to block enzymatic function and neutralize cytotoxicity. Interestingly, we also obtained an anti-A chain Ab that bound with high avidity, blocked enzymatic activity, did not neutralize cytotoxicity, and actually enhanced the in vivo toxicity of ricin. Anti-A chain Abs with moderate avidity had no in vivo effect, nor did any anti-B chain Abs.

In an effort to develop a non-lethal model of ricin toxicosis, we studied the biochemical effects of the administration of ricin in mice.Mice received an intraperitoneal injection of ricin toxin, after which a panel of 21 biochemical parameters was determined. Effect of ricin administration on blood glucose concentration was studied in greater detail. To determine whether results of biochemical analyses correlated with therapeutic manipulations known to protect against ricin toxicosis, the effect of immunization on blood glucose values after ricin administration was studied.Of the biochemical parameters studied, only blood glucose and amylase values were affected by ricin administration. Because blood glucose concentration can be easily and instantaneously measured on 25 to 50 microl of blood, using handheld instruments, this parameter was further evaluated. A dose- and time-related decrease in blood glucose concentration was documented. Mice immunized with ricin had smaller changes in blood glucose concentration than did non-immunized animals after ricin administration.Blood glucose concentration may be used as a surrogate for lethal challenge as a measure of ricin toxicosis after its systemic administration.