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:

  1. To define growth and mutation rates in Mtb during human latency.
  2. To develop and characterize a rabbit model of latency.
  3. 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.