Buruli ulcer disease: Prospects for a vaccine

Scientific Institute of Public Health, Rue Engelandstraat 642, 1180 Brussels, Belgium.
Medical Microbiology and Immunology (Impact Factor: 3.04). 03/2009; 198(2):69-77. DOI: 10.1007/s00430-009-0109-6
Source: PubMed


Buruli ulcer disease (BUD), caused by Mycobacterium ulcerans, is a neglected bacterial infection of the poor in remote rural areas, mostly affecting children. BUD is a mutilating disease leading to severe disability; it is the third most common mycobacterial infection in immunocompetent people after tuberculosis and leprosy. It is most endemic in West Africa, but cases have been reported from more than 30 countries. Treatment with antibiotics is possible, long-lasting and requires injections; there are cases of treatment failures, and the disease is prone to resistance. A vaccine against M. ulcerans would protect persons at risk in highly endemic areas, and could be used as a therapeutic vaccine to shorten the duration of treatment and prevent relapses. There is considerable evidence supporting the notion that generation of a vaccine is feasible. This article reviews the present state of the art with special emphasis on the immunology of the infection and the prospects for development of a vaccine.

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Available from: Caroline Demangel, Apr 18, 2014
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    • "Given the deficient cross-reactive immune response elicited by BCG vaccination during M. ulcerans infection, it has been argued that an M. ulcerans-specific immunization would be more efficient at controlling infection. Indeed, there are differences in genetic and antigenic mycobacterial composition that can result in variations of immunodominant epitopes [38]. Therefore, we evaluated the efficacy of a vaccination protocol with a mycolactone-negative strain of M. ulcerans. "
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    ABSTRACT: Buruli ulcer (BU) is an emerging infectious disease caused by Mycobacterium ulcerans that can result in extensive necrotizing cutaneous lesions due to the cytotoxic exotoxin mycolactone. There is no specific vaccine against BU but reports show some degree of cross-reactive protection conferred by M. bovis BCG immunization. Alternatively, an M. ulcerans-specific immunization could be a better preventive strategy. In this study, we used the mouse model to characterize the histological and cytokine profiles triggered by vaccination with either BCG or mycolactone-negative M. ulcerans, followed by footpad infection with virulent M. ulcerans. We observed that BCG vaccination significantly delayed the onset of M. ulcerans growth and footpad swelling through the induction of an earlier and sustained IFN-γ T cell response in the draining lymph node (DLN). BCG vaccination also resulted in cell-mediated immunity (CMI) in M. ulcerans-infected footpads, given the predominance of a chronic mononuclear infiltrate positive for iNOS, as well as increased and sustained levels of IFN-γ and TNF. No significant IL-4, IL-17 or IL-10 responses were detected in the footpad or the DLN, in either infected or vaccinated mice. Despite this protective Th1 response, BCG vaccination did not avoid the later progression of M. ulcerans infection, regardless of challenge dose. Immunization with mycolactone-deficient M. ulcerans also significantly delayed the progression of footpad infection, swelling and ulceration, but ultimately M. ulcerans pathogenic mechanisms prevailed. The delay in the emergence of pathology observed in vaccinated mice emphasizes the relevance of protective Th1 recall responses against M. ulcerans. In future studies it will be important to determine how the transient CMI induced by vaccination is compromised.
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    ABSTRACT: Bacteria belonging to the genus Mycobacterium can cause several infectious diseases affecting humans and animals. Here, we reviewed the latest advances in the development of DNA vaccines against TB, Buruli ulcer and Johne's disease. Current understanding of the immunity to the respective causative pathogens indicates that the use of DNA vaccines encoding mycobacterial antigens could lead to efficient vaccination strategies. Moreover, characterization of protective mycobacterial antigens has been greatly facilitated by the analysis of immune responses induced after DNA vaccination. In addition, work aiming at optimizing DNA vaccines against mycobacterial diseases and research related to the controversial development of postexposure and therapeutic DNA vaccines are also discussed.
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