title: 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 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.
authors.affiliation: Baylor College of Medicine, Houston, TX, USA.
authors.forename: Wendy A
authors.initials: WA
authors.lastname: Keitel
authors.forename: John J
authors.initials: JJ
authors.lastname: Treanor
authors.forename: Hana M
authors.initials: HM
authors.lastname: El Sahly
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Evans
authors.forename: Scott
authors.initials: S
authors.lastname: Kopper
authors.forename: Vanessa
authors.initials: V
authors.lastname: Whitlow
authors.forename: Cheryl
authors.initials: C
authors.lastname: Selinsky
authors.forename: David C
authors.initials: DC
authors.lastname: Kaslow
authors.forename: Alain
authors.initials: A
authors.lastname: Rolland
authors.forename: Larry R
authors.initials: LR
authors.lastname: Smith
authors.forename: Peggy A
authors.initials: PA
authors.lastname: Lalor
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D000881:Anthrax / Q000097:blood / Q000276:immunology* / Q000517:prevention & control*; D022122:Anthrax Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology; D001408:Bacillus anthracis / Q000276:immunology*; D001427:Bacterial Toxins / Q000235:genetics / Q000276:immunology; D004334:Drug Administration Schedule; D004353:Drug Evaluation, Preclinical; D005260:Female; D006801:Humans; D007273:Injections, Intramuscular; D008252:Macaca fascicularis; D008297:Male; D008875:Middle Aged; D009518:New York; D011817:Rabbits; D013781:Texas; D014611:Vaccination; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*
chemical_list: D022122:Anthrax Vaccines; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; C547296:VCL-AB01 vaccine; D019444:Vaccines, DNA; C030325:anthrax toxin