PROPHYLAXIS AND TREATMENT WITH A MONOCLONAL-ANTIBODY OF TETRODOTOXIN POISONING IN MICE

The ability of a tetrodotoxin (TTX)-specific monoclonal antibody to co nfer passive protection against lethal TTX challenge was investigated. The monoclonal antibody, T20G10, has an estimated affinity for TTX of approximately 10(-9) M and is about 50-fold less reactive with anhydr otetrodotoxin and unreactive with tetrodonic acid by competitive immun oassay. T20G10 specifically inhibited TTX binding in an in vitro radio ligand receptor binding assay, but had no effect on the binding of sax itoxin to the sodium channel on rat brain membranes. In prophylaxis st udies, mice were administered T20G10 via the tail vein 30 min prior to i.p. TTX challenge (10 mu g/kg). Under these conditions, 100 mu g T20 G10 protected 6/6 mice, whereas 3/6 mice were protected with 50 mu g T 20G10. Non-specific control monoclonal antibody did not protect agains t lethality. Therapy studies simulating oral intoxication were perform ed with mice given a lethal dose of TTX by gavage in a suspension of n on-fat dry milk in phosphate-buffered saline. Death occurred within 25 -35 min in 6/6 mice not treated with T20G10. However, 500 mu g T20G10 administered via the tail vein 10-15 min after oral TTX exposure preve nted death in 6/6 mice. Lower doses of mAb conferred less protection.