Passive Immunotherapy for Anthrax Toxin Mediated by an Adenovirus Expressing an Anti-Protective Antigen Single-Chain Antibody

• Published in: Molecular therapy Vol. 11; no. 2; pp. 237 - 244
• Main Authors: Kasuya, Kazuhiko, Boyer, Julie L., Tan, Yadi, Alipui, D. Olivier, Hackett, Neil R., Crystal, Ronald G.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.02.2005; Elsevier Limited
• Subjects: Adenoviridae - genetics; Adenoviruses; Animals; Anthrax; Anthrax Vaccines - genetics; Anthrax Vaccines - immunology; Antibodies, Bacterial - administration & dosage; Antibodies, Bacterial - genetics; Antibodies, Bacterial - immunology; Antigens; Antigens, Bacterial - immunology; Bacterial Toxins - antagonists & inhibitors; Bacterial Toxins - immunology; Biological & chemical terrorism; Drug dosages; Gene Expression - genetics; Gene therapy; Immunization, Passive - methods; Immunotherapy; Infections; Mice; Molecular weight; Monoclonal antibodies; Proteins; Survival Rate; Vaccines; Virulence; New York; United States > US
• ISSN: 1525-0016; 1525-0024
• DOI: 10.1016/j.ymthe.2004.10.018

In the 2001 U.S. bioterror attacks, 33,000 individuals required postexposure prophylaxis, 18 subjects contracted anthrax (11 inhalation, 7 cutaneous), and despite optimal medical therapy, 5 deaths resulted. Rapid protection against anthrax is required in a bioterrorism scenario; this study describes an in vivo gene transfer-based therapy that uses a human adenovirus (Ad)-based vector (AdαPAscAb) encoding a single-chain antibody directed against protective antigen (PA), a critical component of Bacillus anthracis lethal toxin. Following AdαPAscAb administration to mice, anti-PA single-chain antibody and anti-PA neutralizing activity were detected in serum over a 2-week period. Substantial survival advantage from anthrax lethal toxin was conferred by AdαPAscAb following administration from 1 to 14 days prior to toxin challenge, compared to no survival associated with an Ad vector expressing a control single-chain antibody. Passive immunotherapy with an Ad-based vector may be a rapid, convenient approach for protecting a susceptible population against anthrax, including use as an adjunct to antibiotic therapy.