Evaluation of a plasmid DNA-based anthrax vaccine in rabbits, nonhuman primates and healthy adults
Volume 5, Issue 8
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Pages 536 - 544http://dx.doi.org/10.4161/hv.5.8.8725
Authors: Wendy A. Keitel, John J. Treanor, Hana M. El Sahly, Thomas G. Evans, Scott Kopper, Vanessa Whitlow, Cheryl Selinsky, David C. Kaslow, Alain Rolland, Larry R. Smith and Peggy A. Lalor View affiliations
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.
Received: March 6, 2009; Accepted: April 14, 2009