[Immunization against tuberculosis: new vaccination strategies or is there an alternative to BCG?].

Abstract

Consistently high tuberculosis rates in many developing nations, the surprising increase in tuberculosis cases in numerous industrialized countries, together with the emergence of multi-drug-resistant strains of Mycobacterium tuberculosis have sharpened public interest in this ancient scourge. Improved tuberculosis control could best be achieved by an efficacious vaccine. The available attenuated vaccine strain, Mycobacterium bovis BCG, has only limited efficiency. This vaccine is capable of protecting against disseminated miliary tuberculosis in the newborn, but it is unable to prevent stable infection and to cause sterile pathogen eradication. Hence, adult tuberculosis, representing the majority of all tuberculosis cases, is not preventable by BCG vaccination. Due to the extraordinarily high rate of asymptomatic M. tuberculosis infection (1/3 of the total world population) any novel vaccination strategy has to fulfil two major tasks: first, prevention of stable infection, second, eradication of already established infection. T lymphocytes represent the major target for any vaccine strategy, because they serve as central mediators of acquired immunity. They segregate into distinct populations, characterized by different activation conditions and biological functions. These T cell populations do not act independently from, but rather interact with, each other mostly through cytokines. Although CD4 T lymphocytes of T helper 1 type are essential for protection, CD8 T cells expressing cytolytic functions are required, in addition. Perhaps other T cell populations, such as gamma/delta T cells and double negative alpha/beta T cells, also participate. An effective vaccine has to stimulate the precise combination of T cells and cytokines required for the different tasks. It remains to be clarified in how far this can be achieved by a single vaccine.