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

Hum Vaccin. 2009 Aug;5(8):536-44. doi: 10.4161/hv.5.8.8725. Epub 2009 Aug 14.

Abstract

VCL-AB01, a cationic lipid-formulated plasmid DNA (pDNA)-based vaccine that contains genes encoding genetically detoxified Bacillus 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 two 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 one subject. In monkeys that received a 0.6 mg dose three 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, 75% 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.

Publication types

  • Clinical Trial, Phase I
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Animals
  • Anthrax / blood
  • Anthrax / immunology*
  • Anthrax / prevention & control*
  • Anthrax Vaccines / administration & dosage
  • Anthrax Vaccines / adverse effects
  • Anthrax Vaccines / immunology*
  • Antibodies, Bacterial / blood
  • Antigens, Bacterial / genetics
  • Antigens, Bacterial / immunology
  • Bacillus anthracis / immunology*
  • Bacterial Toxins / genetics
  • Bacterial Toxins / immunology
  • Drug Administration Schedule
  • Drug Evaluation, Preclinical
  • Female
  • Humans
  • Injections, Intramuscular
  • Macaca fascicularis
  • Male
  • Middle Aged
  • New York
  • Rabbits
  • Texas
  • Vaccination
  • Vaccines, DNA / administration & dosage
  • Vaccines, DNA / adverse effects
  • Vaccines, DNA / immunology*

Substances

  • Anthrax Vaccines
  • Antibodies, Bacterial
  • Antigens, Bacterial
  • Bacterial Toxins
  • VCL-AB01 vaccine
  • Vaccines, DNA
  • anthrax toxin