抗炭疽人源化单抗在炭疽芽孢致死小鼠模型中的治疗效力评价

Efficacy of a Humanized Monoclonal Antibody in an Anthrax Spore-Challenged Mouse Model

目的:建立炭疽芽孢(疫苗株A16R)攻击DBA/2J小鼠的致死模型,并使用该模型评价抗炭疽人源化单抗5E11的治疗效力。方法:用不同剂量A16R芽孢背部皮下攻击小鼠,计算半数致死剂量(LD_(50));ELISA定量检测5E11在小鼠体内的药代动力学参数;用100倍LD_(50)的芽孢攻击小鼠,攻毒后不同时间用不同剂量的5E11单抗治疗小鼠,观察小鼠存活等情况。结果:A16R芽孢攻击DBA/2J小鼠的LD50为7.8×10～3CFU;5E11在小鼠体内的平均消除半衰期约为7 d;攻毒后1 d给药的几个剂量组能够完全保护,攻毒后2～3 d给药能够提供40%～80%的保护。结论:抗炭疽人源化单抗5E11在芽孢攻击致死小鼠模型中表现出良好的保护效果,具有紧急治疗炭疽芽孢感染导致的急性炭疽的潜力。

Objective: To establish a DBA/2 J mouse model with anthrax spore(anthrax vaccine strain A16 R)challenge, and to evaluate the efficacy of 5 E11 against anthrax in this model. Methods: Mice were challenged with a series of doses of A16 R spores and the median lethal dose(LD_(50)) was calculated. The concentrations of5 E11 in serum were detected by ELISA and afterwards pharmacokinetics parameters were analyzed. All groups of the mice were challenged with 100×LD_(50) spores and different groups were treated with 5 E11 at different time and doses, followed by survival observation. Results: The LD50 of A16 R spore in DBA/2 J mouse was 7.8×10~3 CFU.The mean elimination half-life(t_(1/2)) of 5 E11 in mouse was approximately 7 days. Administration with 5 E11 one day after challenge provided full protection, and the mice administrated two or three days after challenge reached the survival rate 40% to 80%. In addition, the results showed the survival was dose independent. Conclusion:5 E11 can effectively protect mice from anthrax spores and has the potential to provide emergent treatment for acute anthrax.