Passive immunotherapy for anthrax toxin mediated by an adenovirus expressing an anti-protective antigen single-chain antibody.

Abstract

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 (AdalphaPAscAb) encoding a single-chain antibody directed against protective antigen (PA), a critical component of Bacillus anthracis lethal toxin. Following AdalphaPAscAb 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 AdalphaPAscAb 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.

• Authors: Kazuhiko Kasuya, Julie L Boyer, Yadi Tan, D Olivier Alipui, Neil R Hackett, Ronald G Crystal
• Journal: Molecular therapy : the journal of the American Society of Gene Therapy (Mol Ther) Vol. 11 Issue 2 Pg. 237-44 (Feb 2005) ISSN: 1525-0016 [Print] United States
• PMID: 15668135 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Anthrax Vaccines
• Antibodies, Bacterial
• Antigens, Bacterial
• Bacterial Toxins
• anthrax toxin

Topics

• Adenoviridae (genetics)
• Animals
• Anthrax Vaccines (genetics, immunology)
• Antibodies, Bacterial (administration & dosage, genetics, immunology)
• Antigens, Bacterial (immunology)
• Bacterial Toxins (antagonists & inhibitors, immunology)
• Gene Expression (genetics)
• Immunization, Passive (methods)
• Mice
• Survival Rate