Effect of Increasing Toxin Levels on Guineau Pigs Passively Immunized With Human Botulinum Immune Globulin

摘要

Pentavalent Botulinum Toxoid (PBT) vaccine is intended for use as a medical countermeasure for combat troops with the potential for exposure to botulinum toxins on the battlefield. As efficacy for this vaccine cannot be directly demonstrated in traditional clinical trials, the measurement of neutralizing antibodies has been proposed as a serological correlate for protection. Task 97-52 is designed to establish the level of protection afforded by target circulating antibody levels of 0.06 U/I'lL against five serotypes (A- E) of botulinum toxins. Botulism immune globulin (BIG), raised in vaccinated volunteers, was passively administered to guinea pigs at a dosage of 10 U/kg. Based on previous studies, this was the estimated dose necessary to produce approximately 0.06 U/niL in semm 24 hours after administration. Control guinea pigs were given vaccinia immune globulin (VIG) with dosages normalized to IgG content. Neutralizing antibody levels were measured by a mouse bioassay. Twenty- four hours after administration, guinea pigs were challenged with varying doses of botulinum toxins by intramuscular injection to determine protective ratios (median lethal dose-protected: median lethal dose-unprotected). Probit analyses were based on fourteen-day survival data following toxin treatment. Toxin dosages were determined by an in vivo mouse potency assay on each day * of experimentation and expressed in terms of mouse intraperitoneal median lethal dose (MlPLDso) units. At the time of toxin treatment, random samples of guinea pigs were used to measure circulating antibody levels for each of the serotypes.