AdVAV is a replication-deficient adenovirus type 5-vectored vaccine expressing the 83kD protective antigen (PA83) from Bacillus anthracis that is being developed for the prevention of disease caused by inhalation of aerosolized B. anthracis spores. A non-inferiority study comparing the efficacy of AdVAV to the currently licensed anthrax vaccine absorbed (AVA, BioThrax) was performed in New Zealand White (NZW) rabbits using post-challenge survival as the study endpoint (20% non-inferiority margin for survival). Three groups of 32 rabbits were vaccinated with a single intranasal dose of AdVAV (7.5 x 107, 1.5 x 109 or 3.5 x 1010 viral particles). Three additional groups of 32 animals received two doses of either intranasal AdVAV (3.5 x 1010 viral particles) or intramuscular AVA (diluted 1:16 or 1:64) 28 days apart. The placebo group of 16 rabbits received a single intranasal dose of AdVAV formulation buffer. All animals were challenged via the inhalation route with a targeted dose of 200 LD50 of aerosolized B. anthracis Ames spores 70 days after the initial vaccination and were followed for three weeks. PA83 immunogenicity was evaluated by validated toxin neutralizing antibody (TNA) and serum anti-PA83 IgG ELISA assays. All animals in the placebo cohort died from challenge. Three of the four AdVAV dose cohorts tested, including two single dose cohorts, achieved statistical non-inferiority relative to the AVA comparator group with survival rates between 97 – 100%. Vaccination with AdVAV also produced antibody titers with earlier onset and greater persistence as compared to vaccination with AVA.

Read more »