title: Preclinical safety assessment of a recombinant plague vaccine (rF1V).
abstract: 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.
authors.affiliation: DynPort Vaccine Company LLC, A CSC Company, 64 Thomas Johnson Drive Frederick, MD 21702, USA. Email: jprice30@csc.com.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Price
authors.forename: T Scott
authors.initials: TS
authors.lastname: Manetz
authors.forename: Jeffry D
authors.initials: JD
authors.lastname: Shearer
authors.forename: Robert V
authors.initials: RV
authors.lastname: House
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D001426:Bacterial Proteins / Q000276:immunology; D004353:Drug Evaluation, Preclinical; D005260:Female; D008297:Male; D051379:Mice; D010931:Plague Vaccine / Q000008:administration & dosage*; D052899:Pore Forming Cytotoxic Proteins / Q000276:immunology; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000276:immunology; D012867:Skin / Q000187:drug effects / Q000473:pathology; D023422:Skin Irritancy Tests; D014614:Vaccines, Synthetic / Q000008:administration & dosage*
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C043908:LcrV protein, Yersinia; D010931:Plague Vaccine; D052899:Pore Forming Cytotoxic Proteins; D011993:Recombinant Fusion Proteins; D014614:Vaccines, Synthetic; C086725:caf1 protein, Yersinia pestis
keywords: Yersinia pestis; plague; recombinant vaccine