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