Protection against botulinum toxins provided by passive immunization with botulinum human immune globulin: Evaluation using an inhalation model

Pentavalent botulinum toroid adsorbed (ABCDE) vaccine is intended to protec t military personnel from battlefield exposures to botulinum serotypes A-E, To determine the neutralizing antibody levels in serum that are indicative of protection against aerosolized botulinum toxins, a guinea pig model of passive antibody transfer was developed, Botulinum immune globulin (BIG), d erived from plasma of vaccinated volunteers, was administered to guinea pig s by intraperitoneal injection to attain neutralizing antibody levels in se rum of ca. 0.25 U ml(-1). Control groups were treated with vaccinia immune globulin (VIG), with dosages normalized to antibody content, Neutralizing a ntibody levels were determined by a mouse bioassay, Twenty-four hours after BIG treatment, animals were challenged with lethal levels (target of 25 x LCt(50)) of botulinum toxins by an inhalation route. Protection was defined as 80% or greater survival for BIG-treated animals. If protective, additio nal groups were treated with progressively smaller BIG dosages (75% decreas es per iteration) and challenged with 25 x LCt(50) until protection was no longer afforded. Greater than 80% survival was observed at target levels of 0.25 U ml(-1) for all five serotypes, Breakthrough mortality (>20%) was ob served at test levels of 0.05, 0.004, 0.015, 0.014 and 0.003 U ml(-1) for s erotypes A-E, respectively. These results, along with neutralizing antibody measurements from clinical trials, can be used to predict human efficacy f ollowing vaccination with pentavalent botulinum toroid adsorbed (ABCDE) vac cine.