Immune protection against tuberculosis--when is immunotherapy preferable to vaccination?

In view of the limited protection against tuberculosis, especially the infectious forms of pulmonary tuberculosis, afforded by Bacille Calmette-Guérin (BCG) vaccination, attempts are being made to develop more effective alternatives. Many of these attempts are based on the classical strategy of selecting 'protective' epitopes of Mycobacterium tuberculosis to induce immune responses in the vaccinated host. Such strategies, which in the past have been applied very effectively for the prevention of many acute infectious diseases, may not be relevant for a chronic disease in which both pathogen and host have co-evolved so that the majority of infected individuals remain asymptomatic, albeit latently infected, and in which inappropriate, dysregulated, patterns of immune reactivity predispose to, and maintain, the long-term pathological processes in a minority of symptomatic diseased individuals. While immune responses against the causative pathogen are of doubtless importance in the mediation of protection in the asymptomatic majority, we postulate that it is equally, or more, significant for public health to induce the required protective pattern of immune reactivity by immunotherapy in the diseased minority.