Roadmap for the development of candidate vaccine for bTB

What are we trying to achieve and why? What is the problem we are trying to solve?

To gain an improved understanding of how M bovis enters, replicates and survives in and is released from infected cells

What are the scientific and technological challenges
(knowledge gaps needing to be addressed)?

M bovis infects macrophages which are an important contributor to the immune response so establishing how the
bacterium interacts with macrophages is central to identifying the protective mechanisms and how the virus evades them.

What approaches could/should be taken to address the research question?

• M bovis and macrophage gene expression(transcriptome/RNA sequence data) in different in vivo environments
  (macrophages from naïve and immune hosts)
• Compare response where macrophages are infected with different M bovis strains, BCG and M tuberculosis looking at gene responses of the macrophage and the bacterium.
• Comparison of the macrophage-bacteria response following clearance (is infection ever cleared or just walled off?), in latency(this may involve comparative studies involving different breeds or species) and in active infections

What else needs to be done before we can solve this need?

The genome sequence of various M bovis isolates, including BCG

Existing knowledge including successes and failures