Characterization of a Therapeutic Model of Inhalational Anthrax Using an Increase in Body Temperature in New Zealand White Rabbits as a Trigger for Treatment

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 ZealandWhite rabbits exhib-ited 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 humanmonoclonal antibody directed at protective antigen (PA). Ninety percent (9/10) of the treated rabbits survived the lethal inhalational challenge of B. anthracis. Further characteriza-tion 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 bac-teremia and antigenemia (PA in the blood), indicating that SIBT is a suitable trigger to initiate treatment in a therapeutic model of inhalational anthrax. Bacillus anthracis, the etiologic agent of anthrax, is a Gram-positive, spore-forming bacterium that can cause human dis-ease via the gastrointestinal, cutaneous, or inhalation (pulmo-nary) routes, each exhibiting different clinical manifestations of disease, with pulmonary being the most lethal (3). The virulenc