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
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