Project 2
Validation and application of a model of human TB-like latency in rabbits
Goal: To develop a suitable animal model that can help better understand the mechanisms involved in Mtb latency.
Questions addressed:
- How does Mtb replicate and mutate during human and rabbit latency?
- Are there early markers of bacterial clearance in response to chemotherapy and/or a vaccine and immunostimulatory agents?
- What are the correlates of protection from active TB disease?
- Which bacterial factors are essential for latency? Which represent good drug targets?
Specific aims:
- To define growth and mutation rates in Mtb during human latency.
- To develop and characterize a rabbit model of latency.
- To use the rabbit latency model to test immunological and drug interventions to eradicate the latent state.
Significance: A validated rabbit model of latency, along with new tools that allow for latent Mtb to be monitored for growth, persistence and decline at the clonal level will allow pre-clinical testing of new drugs and regimens and immunotherapeutics.
