title: Delayed treatment with W1-mAb, a chimpanzee-derived monoclonal antibody against protective antigen, reduces mortality from challenges with anthrax edema or lethal toxin in rats and with anthrax spores in mice.
abstract: OBJECTIVE
  W1-mAb is a chimpanzee-derived monoclonal antibody to protective antigen that improved survival when administered before anthrax lethal toxin challenge in rats. To better define W1-mAb's efficacy for anthrax, we administered it after initiation of 24-hr infusions of edema toxin and lethal toxin either alone or together in rats or following anthrax spore challenge in mice.
  
  
  METHODS
  W1-mAb or placebo treatment.
  
  
  RESULTS
  In toxin-challenged rats treated with placebo, survival rates were lower with edema toxin (500 μg/kg) compared to lethal toxin either alone (175 μg/kg) or with edema toxin (175 μg/kg each) (8%, 33%, and 32%, respectively), but the median time to death was longer (36, 11, and 9 hrs, respectively) (p ≤ .01 for all comparisons). W1-mAb administered up to 12 hrs after edema toxin and 6 hrs after lethal toxin increased survival and reduced hypotension (p ≤ .01). However, only administration of W1-mAb at 0 hrs improved these variables with lethal toxin and edema toxin together (p ≤ .0002). In C57BL/6J mice challenged with anthrax spores subcutaneously, compared to placebo treatment (0 of 15 animals survived), W1-mAb administered beginning 24 hrs after challenge increased survival (13 of 15 survived) (p ≤ .0001).
  
  
  CONCLUSIONS
  While rapidity of lethality may influence the effectiveness of delayed W1-mAb treatment, these rat and mouse studies provide a basis for further exploring this agent's usefulness for anthrax.
authors.affiliation: Critical Care Medicine Department, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Laith
authors.initials: L
authors.lastname: Altaweel
authors.forename: Zhaochun
authors.initials: Z
authors.lastname: Chen
authors.forename: Mahtab
authors.initials: M
authors.lastname: Moayeri
authors.forename: Xizhong
authors.initials: X
authors.lastname: Cui
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Junwu
authors.initials: J
authors.lastname: Su
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Fitz
authors.forename: Syd
authors.initials: S
authors.lastname: Johnson
authors.forename: Stephen H
authors.initials: SH
authors.lastname: Leppla
authors.forename: Robert
authors.initials: R
authors.lastname: Purcell
authors.forename: Peter Q
authors.initials: PQ
authors.lastname: Eichacker
mesh_terms: D000818:Animals; D000881:Anthrax / Q000188:drug therapy* / Q000209:etiology; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D000942:Antigens, Bacterial / Q000008:administration & dosage*; D001408:Bacillus anthracis / Q000276:immunology*; D001427:Bacterial Toxins / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D007155:Immunologic Factors / Q000008:administration & dosage*; D051379:Mice; D008810:Mice, Inbred C57BL; D002679:Pan troglodytes; D051381:Rats; D017207:Rats, Sprague-Dawley; D013171:Spores, Bacterial
chemical_list: D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D007155:Immunologic Factors; C030325:anthrax toxin