Passive immunotherapy for anthrax toxin mediated by an adenovirus expressing an anti-protective antigen single-chain antibody.
Publication Type | Academic Article |
Authors | Kasuya K, Boyer J, Tan Y, Alipui D, Hackett N, Crystal R |
Journal | Mol Ther |
Volume | 11 |
Issue | 2 |
Pagination | 237-44 |
Date Published | 02/01/2005 |
ISSN | 1525-0016 |
Keywords | Adenoviridae, Antibodies, Bacterial, Antigens, Bacterial, Bacterial Toxins, Gene Expression, Immunization, Passive |
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. |
DOI | 10.1016/j.ymthe.2004.10.018 |
PubMed ID | 15668135 |