Tuberculosis vaccines: the past, present and future.

Tuberculosis still remains a leading infectious cause of death worldwide, although the BCG vaccine has been used for 80 years. There is an urgent need to develop improved BCG or new tuberculosis vaccines. This apparently represents a daunting task, since it will take a long time before a vaccine can be declared to be better than the current BCG vaccine, both in experimental and human studies. The current review takes a brief historic look at the use of current BCG vaccine and provides an overview on what are considered to be the key immunologic criteria that have to be met by a new generation of tuberculosis vaccines. It also provides the most up-to-date information on the latest developments in tuberculosis vaccine research, with a focus on mycobacterial organism-based and Mycobacterium tuberculosis antigen-based vaccines. Consideration is also given to the mucosal route of immunization and 'prime and boost' regimens. This review also presents several important tables, highlighting critical components of antituberculosis immunity, the most commonly tested immune adjuvants, the types of novel tuberculosis antigen-based vaccines and the outcome of different heterologous 'prime and boost' vaccination regimens.