Group | Molecularimmunology

Mycobacterium ulcerans Infection (Buruli ulcer): Towards Improving Control, Diagnosis and Therapy

After tuberculosis and leprosy, Buruli ulcer, caused by M. ulcerans, is the third most common mycobacterial disease, and Western Africa is the world region most affected by this chronic necrotising disease of the skin and the subcutaneous tissue. M. ulcerans is unique among mycobacterial pathogens in that it is mainly extracellular and produces a plasmid-encoded toxin with a polyketide-derived macrolide structure, named mycolactone.

Symptoms and Treatment

Mycolactone is believed to play a central role in determining the extracellular localization of the bacteria and modulation of immunological responses to M. ulcerans. Clinical lesions usually start as painless nodules and if left untreated lead to massive destruction of skin and sometimes bone. While surgery has traditionally been the only recommended treatment for BU, in 2004 WHO published provisional guidelines recommending treatment with a combination of rifampicin and streptomycin for 8 weeks.

Our Research

We developed a broad research portfolio comprising clinical, field and laboratory studies. The goals of our research are to improve understanding of the pathogenesis, immunology and transmission of Buruli ulcer, develop methods for early diagnosis, and investigate prospects for improving therapy and vaccine development.
 

P. falciparum: Developing a Synthetic Subunit Candidate Vaccine

Malaria is one of the most serious infectious diseases of humans. New approaches to combat malaria are urgently needed, and a vaccine is predicted to have the greatest impact in addition to being the most cost-effective control measure.

We are developing synthetic peptide structures that induce cross-reactive antibodies against the parent malaria proteins and by coupling them to the surface of immunopotentiating reconstituted influenza virosomes (IRIVs). In addition we are evaluating the use of so fare uncharacterized predicted proteins of Plasmodium falciparum as potential new candidate vaccine antigens.

Vaccine Development

One approach is to design a subunit vaccine that incorporates several malaria protein antigens for which there is evidence of protective immunity from epidemiological data or experimental animal challenge models. Development of such subunit vaccines is critically dependent on the availability of an antigen delivery system to drive suitable protein antigen-specific immune responses in humans. Vaccine formulations have to be highly effective, human-compatible and safe. Production of synthetic or recombinant proteins that stably mimic the native structure of the corresponding malaria antigens to induce effective humoral immune responses is a further major challenge.

Our research

We are addressing both problems by developing synthetic peptide structures that induce cross-reactive antibodies against the parent malaria proteins and by coupling them to the surface of immunopotentiating reconstituted influenza virosomes (IRIVs). In addition we are evaluating the use of so fare uncharacterized predicted proteins of Plasmodium falciparum as potential new candidate vaccine antigens.

European Malaria Vaccine Development Association (EMVDA)
 

Meningococcal Meningitis: Clonal Waves of Colonisation and Disease in the Meningitis Belt of Sub-Saharan Africa

Bacterial meningitis is a medical emergency and remains one of the major health problems in Sub-Saharan Africa. The three most important agents are Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae. All three pathogens are common colonizers of the human nasopharynx, invasive disease is usually a rare event.

The bacterial meningitis project involves longitudinal studies of the molecular epidemiology of comparatively carriage and disease of N. meningitidis and S. pneumoniae. The studies are being carried out in Northern Ghana and Burkina Faso and aim to enhance the understanding of the dynamics of meningitis epidemics in the African Meningitis Belt. The results provide important background information for the evaluation and introduction of new conjugate vaccines against meningococcal and pneumococcal infections in Africa.