Antibacterial vaccines: impact of antigen handling and immune response

The emerging awareness that diseases caused by bacterial pathogens cannot be vanquished by chemotherapy alone has recalled interest in the generation of novel vaccines. Vaccines have proven their efficacy for the bacterial pathogens that are controlled by antibodies. In contrast, satisfactory vaccines are not available for intracellular bacteria that are under the control of T lymphocytes. This review describes the T cell populations that must be activated by successful vaccines against intracellular bacteria and discusses parameters that need to be fulfilled by protective T cell antigens. These parameters include: (a) the intracellular localization of the pathogen with major effect on antigen presentation and stimulation of distinct T cell subsets and (b) the antigen display which markedly influences kinetics of T cell activation. Using tuberculosis as an example, the advantages and disadvantages of second-generation vaccine candidates are discussed.