Evaluation of a plasmid DNA-based anthrax vaccine in rabbits, nonhuman primates and healthy adults

 Abstract

VCL-AB01, a cationic lipid-formulated plasmid DNA (pDNA)-based vaccine that contains genes encoding genetically detoxified B. anthracis protective antigen (PA) and lethal factor (LF), was assessed in a Phase 1, dose-escalating clinical trial in healthy adults for safety and immunogenicity, and in nonhuman primates  for immunogenicity and efficacy against challenge with a lethal dose of B. anthracis spores.  Healthy 18-45 year old subjects were randomly assigned to receive either the investigational vaccine containing 0.2 mg, 0.6 mg, or 2 mg of total pDNA per dose, or saline placebo, administered at 0, 1, and 2 months.  The 0.2 mg and 0.6 mg dose levels were generally well tolerated; however, dose-limiting reactogenicity was observed among subjects given the first 2 mg dose and the remaining 2 injections in the 2 mg group were reduced to 0.6 mg.  Dose-related increases in seroconversion frequencies were observed. Overall, 10%, 33.3% and 80% of subjects in the 0.2, 0.6 and 2 mg groups, respectively, developed antibodies to PA and/or LF as measured by ELISA; however, antibodies with toxin neutralizing activity (TNA) were detected in only 1 subject.  In monkeys that received a 0.6 mg dose 3 times at 2 week intervals, low levels of antibodies were detected by ELISA but not by the TNA assay in all animals just prior to challenge.  Despite the absence of TNA, 3/4 animals survived the lethal challenge.  In summary, VCL-AB01 was generally well tolerated in humans at a dose that provided immunity in monkeys despite the lack of robust TNA titers in either species.

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Pages
536 - 544
doi
10.4161/hv.5.8.8725
Type
Research Paper
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Evaluation of a plasmid DNA-based anthrax vaccine in rabbits, nonhuman primates and healthy adults