title: Preclinical safety assessment of recombinant botulinum vaccine A/B (rBV A/B).
abstract: A recombinant botulinum vaccine (rBV A/B) is being developed to protect adults 18-55 years of age from fatal botulism caused by inhalational intoxication with botulinum neurotoxin complex (BoNT) serotype A, subtype A1 (BoNT/A1) and BoNT serotype B, subtype B1 (BoNT/B1). Fundamental to the advanced development process is an initial demonstration of product safety in animals. A comprehensive series of studies was conducted to evaluate the general toxicity, neurobehavioral toxicity and local reactogenicity of the rBV A/B vaccine prior to first use in humans. Toxicity was evaluated in CD-1 mice vaccinated with control material and three dosages of rBV A/B with or without Alhydrogel(®) by intramuscular (IM) injection on Study Days 0, 28, 56 and 70 in a volume of 100μL. Total immunizing protein given in each dose was either 0, 2, 4 or 8 μg/animal. Local reactogenicity was evaluated in mice at the dosages given and in New Zealand white (NZW) rabbits using the same injection volume (0.5 mL) and formulations (10, 20 and 40 g/mL total antigen with 0.2% (w/v) Alhydrogel(®)) intended for human use. The rBV A/B vaccine produced no apparent systemic or neurobehavioral toxicity and only transient mild inflammation at the injection site. Together these results indicated a favorable safety profile for rBV A/B and supported its use in a Phase 1 clinical trial.
authors.affiliation: DynPort Vaccine Company LLC, A CSC Company, Frederick, MD 21702, USA. jshearer2@csc.com
authors.forename: Jeffry D
authors.initials: JD
authors.lastname: Shearer
authors.forename: T Scott
authors.initials: TS
authors.lastname: Manetz
authors.forename: Robert V
authors.initials: RV
authors.lastname: House
mesh_terms: D000818:Animals; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000276:immunology / Q000633:toxicity*; D001905:Botulinum Toxins / Q000633:toxicity*; D001906:Botulism / Q000517:prevention & control*; D004353:Drug Evaluation, Preclinical; D005260:Female; D008297:Male; D051379:Mice; D011817:Rabbits; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology / Q000633:toxicity
chemical_list: D001428:Bacterial Vaccines; D014614:Vaccines, Synthetic; D001905:Botulinum Toxins