Human monoclonal antibody AVP-21D9 to protective antigen reduces dissemination of the Bacillus anthracis Ames strain from the lungs in a rabbit model.
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.
Peterson
Johnny W
JW
Department of Microbiology and Immunology, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-1070, USA. johnny.peterson@utmb.edu
Comer
Jason E
JE
Baze
Wallace B
WB
Noffsinger
David M
DM
Wenglikowski
Autumn
A
Walberg
Kristin G
KG
Hardcastle
Jason
J
Pawlik
Jennifer
J
Bush
Kathryn
K
Taormina
Joanna
J
Moen
Scott
S
Thomas
John
J
Chatuev
Bagram M
BM
Sower
Laurie
L
Chopra
Ashok K
AK
Stanberry
Lawrence R
LR
Sawada
Ritsuko
R
Scholz
Wolfgang W
WW
Sircar
Jagadish
J
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
D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; C030325:anthrax toxin