title: Characterization of a therapeutic model of inhalational anthrax using an increase in body temperature in New Zealand white rabbits as a trigger for treatment.
abstract: The development of an appropriate animal therapeutic model is essential to assess the potential efficacy of therapeutics for use in the event of a Bacillus anthracis exposure. We conducted a natural history study that showed New Zealand White rabbits exhibited a significant increase in body temperature (SIBT), changes in hematologic parameters, and increases in C-reactive protein and succumbed to disease with an average time to death of approximately 73 h following aerosol challenge with B. anthracis Ames spores. The SIBT was used as a trigger to treat with a fully human monoclonal antibody directed at protective antigen (PA). Ninety percent (9/10) of the treated rabbits survived the lethal inhalational challenge of B. anthracis. Further characterization investigated the protective window of opportunity for anti-PA antibody administration up to 12 h post-onset of SIBT. Eighty-three percent (5/6) of the rabbits treated at SIBT and 100% (6/6) of those treated at 6 h after SIBT survived challenge. Only 67% (4/6) of the rabbits treated at 12 h after SIBT survived. The increase in body temperature corresponded with both bacteremia and antigenemia (PA in the blood), indicating that SIBT is a suitable trigger to initiate treatment in a therapeutic model of inhalational anthrax.
authors: Battelle, Columbus, OH, USA. comerj@battelle.org
authors: Jason E
authors: JE
authors: Comer
authors: Bryan D
authors: BD
authors: Ray
authors: Lisa N
authors: LN
authors: Henning
authors: Gregory V
authors: GV
authors: Stark
authors: Roy E
authors: RE
authors: Barnewall
authors: Jason M
authors: JM
authors: Mott
authors: Gabriel T
authors: GT
authors: Meister
mesh_terms: D000818:Animals; D000881:Anthrax / Q000473:pathology* / Q000628:therapy*; D000907:Antibodies, Bacterial / Q000008:administration & dosage; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000942:Antigens, Bacterial; D001408:Bacillus anthracis / Q000472:pathogenicity*; D001427:Bacterial Toxins / Q000037:antagonists & inhibitors; D015415:Biomarkers; D001773:Blood Cells / Q000502:physiology; D002097:C-Reactive Protein / Q000032:analysis; D004195:Disease Models, Animal; D005260:Female; D005334:Fever / Q000175:diagnosis*; D007167:Immunotherapy / Q000379:methods; D008297:Male; D011817:Rabbits; D016019:Survival Analysis; D013997:Time Factors
chemical_list: D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D015415:Biomarkers; C030325:anthrax toxin; D002097:C-Reactive Protein