Vaccination strategies against intracellular microbes

Leishmaniasis, malaria, tuberculosis, leprosy, typhoid and listeriosis are infections diseases which, together, cause enormous public health problems throughout the world. The etiologic agents of these diseases, Leishmania ssp., Plasmodium ssp., Mycobacterium tuberculosis, Mycobacterium leprae, Salmonella typhi/S. paratyphi or Listeria monocytogenes, respectively, are endowed with the capacity to utilize the intracellular habitat of various host cells, including macrophages, erythrocytes and liver cells. This intracellular habitat effectively protects them from antibody-mediated defence mechanisms, so that T lymphocytes are required for acquisition of antimicrobial protection. Protective immunity is best induced by viable vaccines, whereas soluble proteins are generally insufficient. In this review we will focus on immunity to tuberculosis and on the use of viable recombinant vaccines as multivalent carrier systems for the vaccination against various intracellular microbial infections. We will discuss new strategies to improve N, bovis BC and S. typhimurium aroA super(-) by genetic engineering, in order to evoke optimum protection.