The Department of infectious diseases play a key role in the LUMC “Research Profile” of “Immunity, Infection and Tolerance " and in the Center for Infectious Diseases together with the Department of Medical Microbiology and Department of Parasitology. It is well embedded within the overall LUMC profiling areas. The Department collaborates with numerous partners within LUMC and Leiden University.
The theme immunodeficiencies is a clinically important component of the research program. This includes the molecular-genetic identification of new disorders using immunological and molecular-genetic diagnostic technologies, and the treatment of and research into (new) cellular immunodeficiencies. These efforts are directly related to the TRF of the Department. Moreover, the vaccination and travel clinic provide optimal vaccination and counselling schemes to out-patients with impaired immunity, due to e.g. immunosuppressive treatments. Research activities at the vaccination clinic include the study the efficacy of (modified) active immunisation schedules to induce protective immunity in immunosuppressed travellers, in particular those treated with monoclonal antibodies, and to explore the efficacy and safety of alternative routes of vaccine administration. Fundamental research in these areas will focus on biochemical interventions to improve the immune response and on biomarkers which predict a solid memory response.
Tuberculosis research is a major theme in the research program. The TB research is clinical, translational and fundamental in nature and includes partly humanized animal models of TB. Research efforts aim to develop better vaccines and diagnostic, immunologic, transcriptomic and metabolic “biomarker signatures”, and have led to a number of first-in-man clinical studies with newly developed, molecularly defined synthetic TB vaccines. Systems biology, chemical genetics, transcriptomics, metabolomics and immunomic approaches are used to identify the key cellular signalling pathways in host defense to intracellular pathogens in general, and to M. tuberculosis and Salmonellae in particular. Correlates of protection and prospective correlates of risk of developing TB are being identified. Moreover, there is increasing interest in the areas of co-infections (helminth infections; HIV) and co-morbidities such as type-2 diabetes, a major newly identified risk factor for TB. Extensive international collaborative networks have been established, which include leading partners from EU, US and TB endemic areas/countries (SA, Gambia, Ethiopia, Indonesia, etc.).
Leprosy research has been a major research theme at the LUMC since the 1970s. The current research is focussed on the discovery of M. leprae-specific antigens, and the identification of immune-, metabolic and transcriptomic host biomarker profiles for early diagnosis of infection, predicting leprosy reactions and disease development vs protection. Collaborations with endemic field sites within the three main continents reporting leprosy are firmly established (Brazil, Bangladesh, Ethiopia, Nepal, India). In collaboration with the LUMC Dept. Molecular Cell Biology, user-friendly, field-applicable, first generation lateral flow tests are developed based on discriminating host biomarkers and unique M. leprae specific antigens, identified by the Department. Gene expression profiles are being identified as prospective correlates of risk of developing leprosy (reactions). Our Department is the national reference centre for routine serological diagnosis of leprosy, and provides this service also to European partners. In addition, our group has established a large biobank of leprosy patients’ samples including sera, cells and urine.
Research on malaria vaccines
In collaboration with the Department of Parasitology (LUMC) and the Radboud University Medical Center, we challenge volunteers with live Plasmodium falciparum parasites to follow the response to immunisation and infection. The LUMC is at the forefront of research on whole sporozoite malaria vaccines. Candidate genetically attenuated parasite strains that have been developed in the rodent model are translated to P. falciparum by the Leiden Malaria Research Group for clinical studies. Detailed immunological and transcriptomic “biomarker signatures” are being determined to measure vaccine responses using platform technologies (dcRT-MLPA) developed for TB and other diseases with the purpose of advanced immunomonitoring. In the near future vaccine studies with attenuated P. falciparum sporozoite-vaccines are planned and will be executed at the vaccination and travel clinic in LUMC, in close collaboration with the Dept. of Parasitology and Radboud University Medical Center.
Research on antimicrobial peptides
We aim to develop alternatives for antibiotic treatment in the face of the emerging antibiotic-resistant bacterial pathogens. Naturally occurring peptides are selected as lead structures which are further optimized for application and efficacy. Several human 3-D models, such as skin and bladder wall models (see also below), are used to study and select optimal variants peptides. Peptides are being developed for topical applications, such as treatment of MRSA carriage, wound infections, biomaterial-associated infections and urinary tract infections with highly resistant microbes. More recently, efforts have also been initiated to study the epidemiology of nosocomial outbreaks of Clostridium difficile infections (CDI), especially among the elderly with chronic co-morbidities. There are advanced plans to carry out faecal transplantations in patients with relapsing CDI and in patients with colonised with multi-resistant Gram-negative bacteria, which would fit very well with TRF profile of the Department.