BURULIVAC

Identification and development of vaccine candidates for Buruli Ulcer Disease

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 Obiettivo del progetto (Objective)

'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 and 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.'

Introduzione (Teaser)

Prophylactic or preventive vaccination has provided treatment solutions for many infectious diseases. Based on this, EU and African researchers joined forces to develop novel vaccine candidates against the neglected Buruli ulcer disease (BUD).

Descrizione progetto (Article)

BUD is a rare, poverty-related infection caused by Mycobacterium ulcerans that predominantly affects African children. Patients present with a progressive necrosis of skin, subcutaneous tissue and bone, but the transmission mode of BUD remains elusive.

Scientists on the EU-funded 'Identification and development of vaccine candidates for Buruli Ulcer Disease' (http://www.burulivac.eu (BURULIVAC)) project wished to investigate BUD pathogenesis and immunity mechanisms as well as develop novel therapeutic tools. Central to the project work was the capacity development of partner African institutions with respect to immunological analyses, treatment and disease management.

Among the key findings of the project were the pathophysiological impact of the bacterial mycolactone toxin and the identification of its molecular targets. Using a combination of biochemical assays, cellular imaging and animal models, researchers found that mycolactone interferes with the cell structure by altering its cytoskeleton. Upon infection, this damages the integrity of the epidermis and is responsible for BUD pathogenesis.

Characterisation of patient immune responses indicated that infected individuals have an overall suppressed immune system with reduced levels of multiple chemokines, cytokines and immunoglobulins. This profile was associated with an infection-associated drop of glycolytic and oxidative metabolism.

With respect to therapy, BURULIVAC performed extensive work towards the development of prophylactic vaccines. Live bacteria lacking the mycolactone toxin proved very effective at generating protective immunity against virulent strains of M.ulcerans. Partners also generated monoclonal antibodies against mycolactone, following a careful screening and pre-selection process of candidates for their protective capacity in a mouse model.

Overall, the BURULIVAC study has increased awareness about BUD and raised the infrastructure and technological capacity in affected countries. The commercial development of a lead vaccine against BUD will no doubt provide novel prevention and therapeutic options against this debilitating disease.