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. 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 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). 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.