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

作者：Altaweel Laith^*; Chen Zhaochun; Moayeri Mahtab; Cui Xizhong; Li Yan; Su Junwu; Fitz Yvonne; Johnson Syd; Leppla Stephen H; Purcell Robert; Eichacker Peter Q

来源：Critical Care Medicine, 2011, 39(6): 1439-1447.

DOI：10.1097/CCM.0b013e3182120691

• Bacillus anthracis
• lethal and edema toxins
• protective-antigen-directed mAb
• treatment
• rodent

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.
Interventions: W1-mAb or placebo treatment.
Methods and Main Results: In toxin-challenged rats treated with placebo, survival rates were lower with edema toxin (500 mu g/kg) compared to lethal toxin either alone (175 mu g/kg) or with edema toxin (175 mu g/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).
Conclusion: 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. (Crit Care Med 2011; 39: 1439-1447)

• 出版日期2011-6
• 单位NIH