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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

Wendy A. Keitel

Baylor College of Medicine, Houston, Texas, USA

John J. Treanor

University of Rochester, School of Medicine and Dentistry, Rochester, New York, USA

Hana M. El Sahly

Baylor College of Medicine, Houston, Texas, USA

Thomas G. Evans

Novartis, Cambridge, Massachusetts, USA

Scott Kopper

Quintiles, Redmond, Washington, USA

Vanessa Whitlow

Synteract, Incorporated, Carlsbad, California, USA

Cheryl Selinsky

Translational Genomics Research Institute, Phoenix, Arizona, USA

David C. Kaslow

Merck Research Laboratories; North Wales, Pennsylvania USA

Alain Rolland

Vical Incorporated, San Diego, California, USA

Larry R. Smith

Corresponding author: lsmith@vical.com
Vical Incorporated, San Diego, CA

Peggy A. Lalor

Histion, LLC, Everett, Washington, USA

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.

Received: March 6, 2009; Accepted: April 14, 2009

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