Protection against botulinum toxins provided by passive immunization with botulinum human immune globulin: evaluation using an inhalation model.
Pentavalent botulinum toxoid adsorbed (ABCDE) vaccine is intended to protect 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), derived from plasma of vaccinated volunteers, was administered to guinea pigs by intraperitoneal injection to attain neutralizing antibody levels in serum of ca. 0.25 U ml(-1). Control groups were treated with vaccinia immune globulin (VIG), with dosages normalized to antibody content. Neutralizing antibody 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, additional groups were treated with progressively smaller BIG dosages (75% decreases 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 observed at test levels of 0.05, 0. 004, 0.015, 0.014 and 0.003 U ml(-1) for serotypes A-E, respectively. These results, along with neutralizing antibody measurements from clinical trials, can be used to predict human efficacy following vaccination with pentavalent botulinum toxoid adsorbed (ABCDE) vaccine.
Gelzleichter
T R
TR
Battelle Memorial Institute, Medical Research and Evaluation Facility Columbus, OH, USA.
Myers
M A
MA
Menton
R G
RG
Niemuth
N A
NA
Matthews
M C
MC
Langford
M J
MJ
D000280:Administration, Inhalation; D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology*; D001905:Botulinum Toxins / Q000276:immunology* / Q000633:toxicity; D006168:Guinea Pigs; D006801:Humans; D007116:Immunization, Passive; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D014616:Vaccinia virus / Q000276:immunology
D000907:Antibodies, Bacterial; D001905:Botulinum Toxins