Late treatment with a protective antigen-directed monoclonal antibody improves hemodynamic function and survival in a lethal toxin-infused rat model of anthrax sepsis

Xizhong Cui, Yan Li, Mahtab Moayeri, Gil H. Choi, G. M. Subramanian, Xuemei Li, Michael Haley, Yvonne Fitz, Jing Feng, Steven M. Banks, Stephen H. Leppla, Peter Q. Eichacker

Research output: Contribution to journalArticle

Abstract

Background. In animal models, treatment with 5H3, a fully human protective antigen-directed monoclonal antibody (PA-MAb), improved survival when administered close to the time of Bacillus anthracis lethal toxin (LeTx) bolus or live bacterial challenge. However, treatment with PA-MAb would be most valuable clinically if it were beneficial even when administered after the onset of shock and lethality due to LeTx. Methods. We investigated the effects of PA-MAb versus placebo administered in rats (n = 324) at the time of or 3, 6, 9, or 12 h after the initiation of a 24-h LeTx infusion. Results. In rats receiving placebo, mean arterial blood pressure (MBP) and heart rate (HR) were decreased in nonsurvivors, compared with those in survivors, at 6 h and then worsened further, with lethality first evident at 8 h (median, 16 h; range, 8-152 h). At each treatment time, survival rates were greater for PA-MAb than for placebo, although improvement was decreased at later treatment times (P = .001, for the effect of time). Compared with placebo, PA-MAb significantly increased MBP during the 12 h after the initiation of treatment, but the increase was greatest for treatment at 3 h; similarly, PA-MAb significantly increased HR at all treatment times. Conclusion. In this rat model, improvements in outcome due to PA-MAb were significant when it was administered up to 6 h (and approached significance when administered up to 12 h) after initial exposure to LeTx. Clinically, PA-MAb may be beneficial even when administered after the onset of shock and lethality due to LeTx.

Original languageEnglish (US)
Pages (from-to)422-434
Number of pages13
JournalJournal of Infectious Diseases
Volume191
Issue number3
DOIs
StatePublished - Feb 1 2005

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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    Cui, X., Li, Y., Moayeri, M., Choi, G. H., Subramanian, G. M., Li, X., Haley, M., Fitz, Y., Feng, J., Banks, S. M., Leppla, S. H., & Eichacker, P. Q. (2005). Late treatment with a protective antigen-directed monoclonal antibody improves hemodynamic function and survival in a lethal toxin-infused rat model of anthrax sepsis. Journal of Infectious Diseases, 191(3), 422-434. https://doi.org/10.1086/427189