Translational Baseline Model

The infection of Mycobacterium tuberculosis induces a strong adaptive immune response in murine TB model, which suppress the bacterial replication and maintain the bacterial number at a plateau if the development of immune response is fast and strong enough. A quantitative understanding of this adaptive immune effect over incubation time during infection period is critical in selecting the appropriate murine model for testing TB drugs with different mechanism of action at efficacious dose levels starting at appropriate incubation time, and the development of vaccine and host-directed therapy. BALB/c mouse model has been used as a standard mouse model for decades to test potential new regimens for TB, although there are quite a number of limitations in mimicking the pathophysiology of TB infection in human adults. A baseline model has been developed to quantify the bacterial number in BALB/c mouse model by accounting for the net bacterial growth rate and inhibitory effect of adaptive immune response due to bacterial infection. In this model, both bacterial number and incubation time has been factored in the formulation of adaptive immune effect, so the bacterial infection profile in chronic and acute murine model can both be described using a single mathematic model with distinct adaptive immune effect.