Tuberculosis remains a major health problem worldwide. The disease is caused by Mycobacteriumtuberculosis whose preferred habitat is the host macrophage. The immune response against tuberculosis is mediated by different subsets of T cells including both conventional CD4 and CD8 T cells as well as unconventional CD1 restricted and γδ T cells. The CD1 restricted T cells are particularly remarkable because they recognise the glycolipids abundant in the mycobacterial cell wall. Although a vaccine, M.bovis BCG, is available which protects toddlers against miliary tuberculosis, it is ineffective in preventing pulmonary tuberculosis in adults. Therefore, a novel vaccine is urgently required. Knowledge about the functioning of different T cell populations during infection and disease provides the basis for rational vaccine design. We have constructed a recombinant BCG vaccine which, compared with wild-type BCG, induces superior protection not only against laboratory strains but also against clinical isolates of M. tuberculosis.
- BCG, bacille Calmette Guérin
- hly, listeriolysin
- MDR, multidrug resistance
- MHC, major histocompatibility complex
- Mycobacterium tuberculosis
- vaccine design
- BCG vaccine
- phagosome maturation
- T cell
- major histocompatibility complex
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Financial support for the experimental work done in my laboratory is gratefully acknowledged from: EU integrated project TB-VAC, BMBF competence networks “Structural genomics of M. tuberculosis”, “Bacterial proteomics”, “Proteome analysis of membrane-bound proteins”, NGFN (Nationales Genomforschungsnetz) “Genomics of bacterial pathogens”, DFG priority programme “Novel vaccination strategies”, and DFG SFB 421 “Protective and pathologic consequences of antigen processing”.
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