Passive immunotherapy for anthrax toxin mediated by an adenovirus expressing an anti-protective antigen single-chain antibody.
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.
Kasuya
Kazuhiko
K
Department of Genetic Medicine, Weill Medical College of Cornell University, New York, NY 10021, USA.
Boyer
Julie L
JL
Tan
Yadi
Y
Alipui
D Olivier
DO
Hackett
Neil R
NR
Crystal
Ronald G
RG
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D022122:Anthrax Vaccines / Q000235:genetics / Q000276:immunology; D000907:Antibodies, Bacterial / Q000008:administration & dosage / Q000235:genetics* / Q000276:immunology*; D000942:Antigens, Bacterial / Q000276:immunology*; D001427:Bacterial Toxins / Q000037:antagonists & inhibitors* / Q000276:immunology*; D015870:Gene Expression / Q000235:genetics*; D007116:Immunization, Passive / Q000379:methods*; D051379:Mice; D015996:Survival Rate
D022122:Anthrax Vaccines; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; C030325:anthrax toxin