ABSTRACT
The outcome of infection with Mycobacterium tuberculosis is crucially dependent on the immune response of the host. Most individuals mount a response that is sufficient to prevent progression to disease but may allow persistence of viable bacteria in the form of a latent infection. Around 10% of individuals exposed toM. tuberculosis develop clinical tuberculosis (TB), either as a result of failure to control the initial infection or due to reinfection or reactivation of latent infection (1). This secondary disease pathway highlights a major challenge for TB vaccines. The hallmark of the adaptive immune system is its ability to learn from an initial infection how to mount a rapid and effective response when reexposed to the same pathogen. Classically, vaccination mimics the learning process associated with natural infection. Development of secondary disease in individuals who had contained a primary infection with M. tuberculosis shows that the robust learning process seen for a disease like smallpox does not always occur for TB (1). Similarly, individuals who have been cured of TB remain susceptible to reinfection and further disease (2).
