Mechanistic Modeling of Mycobacterium tuberculosis Infection in Murine Models for Drug and Vaccine Efficacy Studies.
Mechanistic Modeling of Mycobacterium tuberculosis Infection in Murine Models for Drug and Vaccine Efficacy Studies.
复制标题
用于药物和疫苗功效研究的小鼠模型中结核分枝杆菌感染的机制模型。
DOI：
10.1128/aac.01727-19
复制
发表时间：
2020
影响因子：
4.9
通讯作者：
Savic,RadaM
中科院分区：
文献类型：
--
作者：
Zhang,Nan;Strydom,Natasha;Tyagi,Sandeep;Soni,Heena;Tasneen,Rokeya;Nuermberger,EricL;Savic,RadaM
结核病（TB）药物、治疗方案和疫苗的开发严重依赖于临床前动物实验，而细菌和免疫反应动力学的量化对于了解药物和疫苗的有效性至关重要。建立了一个基于机制的模型来描述结核分枝杆菌H37 Rv在BALB/c和无胸腺裸鼠中随时间的感染，该模型包括细菌复制、细菌死亡和适应性免疫效应。细菌负荷和孵育时间的S形函数最好地描述了适应性免疫效果。证明该基线模型效用的应用表明：（i）适应性免疫应答对吡嗪酰胺（PZA）药物疗效的重要影响，（ii）化疗停止后复发的小鼠中持续的适应性免疫效应，以及（iii）M.结核病的挑战这些发现证明了我们的模型用于描述M的实用性。结核病感染和相应的适应性免疫动力学，用于评估结核病药物、治疗方案和疫苗的疗效。
Tuberculosis (TB) drug, regimen, and vaccine development rely heavily on preclinical animal experiments, and quantification of bacterial and immune response dynamics is essential for understanding drug and vaccine efficacy. A mechanism-based model was built to describe Mycobacterium tuberculosis H37Rv infection over time in BALB/c and athymic nude mice, which consisted of bacterial replication, bacterial death, and adaptive immune effects. The adaptive immune effect was best described by a sigmoidal function on both bacterial load and incubation time. Applications to demonstrate the utility of this baseline model showed (i) the important influence of the adaptive immune response on pyrazinamide (PZA) drug efficacy, (ii) a persistent adaptive immune effect in mice relapsing after chemotherapy cessation, and (iii) the protective effect of vaccines after M. tuberculosis challenge. These findings demonstrate the utility of our model for describing M. tuberculosis infection and corresponding adaptive immune dynamics for evaluating the efficacy of TB drugs, regimens, and vaccines.