title: Human monoclonal antibody AVP-21D9 to protective antigen reduces dissemination of the Bacillus anthracis Ames strain from the lungs in a rabbit model.
abstract: Dutch-belted and New Zealand White rabbits were passively immunized with AVP-21D9, a human monoclonal antibody to protective antigen (PA), at the time of Bacillus anthracis spore challenge using either nasal instillation or aerosol challenge techniques. AVP-21D9 (10 mg/kg) completely protected both rabbit strains against lethal infection with Bacillus anthracis Ames spores, regardless of the inoculation method. Further, all but one of the passively immunized animals (23/24) were completely resistant to rechallenge with spores by either respiratory challenge method at 5 weeks after primary challenge. Analysis of the sera at 5 weeks after primary challenge showed that residual human anti-PA levels decreased by 85 to 95%, but low titers of rabbit-specific anti-PA titers were also measured. Both sources of anti-PA could have contributed to protection from rechallenge. In a subsequent study, bacteriological and histopathology analyses revealed that B. anthracis disseminated to the bloodstream in some naïve animals as early as 24 h postchallenge and increased in frequency with time. AVP-21D9 significantly reduced the dissemination of the bacteria to the bloodstream and to various organs following infection. Examination of tissue sections from infected control animals, stained with hematoxylin-eosin and the Gram stain, showed edema and/or hemorrhage in the lungs and the presence of bacteria in mediastinal lymph nodes, with necrosis and inflammation. Tissue sections from infected rabbits dosed with AVP-21D9 appeared comparable to corresponding tissues from uninfected animals despite lethal challenge with B. anthracis Ames spores. Concomitant treatment with AVP-21D9 at the time of challenge conferred complete protection in the rabbit inhalation anthrax model. Early treatment increased the efficacy progressively and in a dose-dependent manner. Thus, AVP-21D9 could offer an adjunct or alternative clinical treatment regimen against inhalation anthrax.
authors: Department of Microbiology and Immunology, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-1070, USA. johnny.peterson@utmb.edu
authors: Johnny W
authors: JW
authors: Peterson
authors: Jason E
authors: JE
authors: Comer
authors: Wallace B
authors: WB
authors: Baze
authors: David M
authors: DM
authors: Noffsinger
authors: Autumn
authors: A
authors: Wenglikowski
authors: Kristin G
authors: KG
authors: Walberg
authors: Jason
authors: J
authors: Hardcastle
authors: Jennifer
authors: J
authors: Pawlik
authors: Kathryn
authors: K
authors: Bush
authors: Joanna
authors: J
authors: Taormina
authors: Scott
authors: S
authors: Moen
authors: John
authors: J
authors: Thomas
authors: Bagram M
authors: BM
authors: Chatuev
authors: Laurie
authors: L
authors: Sower
authors: Ashok K
authors: AK
authors: Chopra
authors: Lawrence R
authors: LR
authors: Stanberry
authors: Ritsuko
authors: R
authors: Sawada
authors: Wolfgang W
authors: WW
authors: Scholz
authors: Jagadish
authors: J
authors: Sircar
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D000881:Anthrax / Q000382:microbiology / Q000473:pathology / Q000517:prevention & control* / Q000635:transmission; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000942:Antigens, Bacterial / Q000276:immunology*; D001408:Bacillus anthracis / Q000276:immunology* / Q000472:pathogenicity / Q000502:physiology; D001427:Bacterial Toxins / Q000276:immunology*; D004195:Disease Models, Animal; D006801:Humans; D008168:Lung / Q000382:microbiology* / Q000473:pathology; D011817:Rabbits; D013171:Spores, Bacterial / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; C030325:anthrax toxin