Pathologie diagnostique : accès libre

Abstrait

Detrimental Role of ‘Decoy’ Constituents in Tuberculosis Vaccination

Juraj

Infection with Mycobacterium tuberculosis (Mtb) is being continually transmitted by cases with active pulmonary Tuberculosis (TB), prior to their late detection. Consequently, TB remains a major global health problem, despite its effective, though protracted, sterilizing chemotherapy. The widely used vaccination with attenuated viable Mycobacterium bovis Bacillus Calmette Guerin (BCG) is known to be protective against meningitis and disseminated TB in children, but not against the most common, reactivated pulmonary disease in adults. Therefore, research and development toward a more effective vaccine has been targeted by many scientists for a number of decades. However, testing of the molecularly defined vaccine candidates in experimental models has been done mostly following BCG priming of the test animals on the grounds, that it might be problematic to withdraw the well-established BCG vaccination of human populations in several countries, though not in the USA. The possible downside of this ‘prime boost’ approach to vaccine testing, as well as the expression of protective subunits in modified mycobacterial constructs has recently been debated on the grounds, that BCG might have retained some of the antigenic and immunomodulatory ‘decoy’ constituents, which evolved in support of mycobacterial pathogenicity. This may involve evasion from natural host resistance and evolutionary selection of genetically permissive immunodominant epitopes, leading to immune responses which sustain a long persisting form of latent infection.