Preclinical safety assessment of a recombinant plague vaccine (rF1V).

A recombinant vaccine (rF1V) is being developed to protect adults 18 to 55 years of age from fatal pneumonic plague caused by aerosolized Yersinia pestis. A comprehensive series of studies was conducted to evaluate the general toxicity and local reactogenicity of the rF1V vaccine prior to first use in humans. Toxicity was evaluated in CD-1 mice vaccinated with control material and three dosage concentrations of rF1V with or without Alhydrogel(®) by intramuscular (IM) injection on Study Days 1, 29, 57 and 71 in a volume of 0.1 mL. Total immunizing protein given in each dose was 0, 20 or 60 μg/animal. Local reactogenicity was evaluated in mice at the dosages given and in New Zealand white (NZW) rabbits using the same injection volume and formulations (40, 80, 160 and 320 μg/mL total antigen and 0.3% (w/v) Alhydrogel(®)) intended for human use (0.5 mL). The rF1V vaccine produced no apparent systemic toxicity and only transient edema and erythema at the injection site. Together these results indicated a favorable safety profile for rF1V and supported its use in a Phase 1 clinical trial.