Identification and development of vaccine candidates for Buruli Ulcer Disease
Keywords: protein subunit vaccines, attenuated live vaccines, mycobacterial infection, Mycobacterium ulcerans, tropical medicine, immune response, immunity
Buruli ulcer disease (BUD), caused by Mycobacterium ulcerans, is a neglected bacterial infection of the poor in remote rural areas, mostly affecting children. BUD, the third most common mycobacterial disease in immunocompetent humans after tuberculosis and leprosy, is most endemic in West Africa, but cases have been reported from more than 30 countries. BUD is a mutilating disease leading to severe disability. Treatment with antibiotics is possible but is long-lasting, requires injections, shows treatment failures and drug resistance may occur. A vaccine against M. ulcerans would protect persons at risk in highly endemic areas and could be used as a therapeutic vaccine to shorten duration of treatment and to prevent relapses.
The general objective of BuruliVac is to identify and develop novel vaccine candidates suitable for translation into clinical application. This objective will be achieved by a multidisciplinary approach involving among others basic and applied research in immunology, bioinformatics, molecular genetics, tropical medicine, microbiology and clinical bacteriology.
As currently no existing vaccine lead candidate is available, the consortium will identify and develop new vaccine candidates of different types, will evaluate them using bioinformatics, applied genomics and proteomics and will subject them to consecutive test systems. For evaluation of vaccine candidates regarding their application in humans, the consortium will also study the immune response and disease immunopathology to define correlates of protection. Essential pre-clinical testing in vitro and in vivo will select a small number of candidates that is amenable to be introduced into clinical studies.
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Protection has to be achieved against this infectious disease that is caused by a toxin-producing bacterium in rural areas of Africa that needs long-time antibiotic treatment and sometimes extensive surgery. Relapses are common. Protection by avoidance is not possible as the mode of infection is unclear.
To identify constituents of M. ulcerans or attenuated strains of M. ulcerans that can be used as a prophylactic or therapeutic vaccine. In the course of these studies extensive capacity building will be performed in the African partner institutions concerning both scientific work and diagnostic and clinical management.
Proteins of the causing bacterium M. ulcerans will be identified that can be used as a vaccine, and attenuated safe strains of M. ulcerans will be generated that can be used as a life vaccine. The African partner institutions will in a position to perform immunological monitoring of patients and molecular diagnostic of the infection.
A vaccine against BUD can be used in people at special risk or concomitant with treatment. The scientific principles underlying this vaccine can be applied to other mycobacterial infections.