Preclinical safety assessment of recombinant botulinum vaccine A/B (rBV A/B).
Vaccine
; 30(11): 1917-26, 2012 Mar 02.
Article
em En
| MEDLINE
| ID: mdl-22269871
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Toxinas Botulínicas
/
Botulismo
/
Vacinas Bacterianas
Limite:
Animals
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article