New strategies against an old plague: genetically engineered tuberculosis vaccines

The failure of BCG vaccination to control the global tuberculosis epidemic and the spread of multidrug resistance underline the need for a better vacc ine. Recent advances in molecular microbiology, gene therapy, and, last but not least, immunobiology, provide a rational basis for the development of more efficient vaccines against tuberculosis. The complete sequencing of th e M. tuberculosis genome marked a turning point in tuberculosis vaccine res earch. The advent of genetic vaccination with either naked DNA, live recomb inant, or artificial vaccine vectors holds out great promise of more effici ent immunisation, in particular against intracellular pathogens such as M. tuberculosis. Our new understanding of how the immune response is orchestra ted by dendritic cells makes it possible to design vaccines which specifica lly exploit the functions of these antigen presenting cells. Yet M. tubercu losis has kept many of its secrets, and although functional genomics, molec ular medicine and immunotherapy are evolving rapidly, much empiric search a nd discovery are needed until the "captain of all these men of death" gives up his ghost to biotechnology.