Characterization of a therapeutic model of inhalational anthrax using an increase in body temperature in New Zealand white rabbits as a trigger for treatment

Jason E. Comer, Bryan D. Ray, Lisa N. Henning, Gregory V. Stark, Roy E. Barnewall, Jason M. Mott, Gabriel T. Meister

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1517-1525
Number of pages9
JournalClinical and Vaccine Immunology
Volume19
Issue number9
DOIs
StatePublished - Sep 2012

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Clinical Biochemistry
  • Microbiology (medical)

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