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- clinical and immunological features of leprosy | British Medical Bulletin | Oxford Academic.
- Recognition of M. leprae antigens.
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A A Janson. Forgot your user name or password? Previous Next. Back to top. In this issue The Journal of Immunology Vol. Download PDF. Article Alerts. Email Article.
HLA and Infectious Diseases
Thank you for your interest in spreading the word about The Journal of Immunology. You are going to email the following A systematic molecular analysis of the T cell-stimulating antigens from Mycobacterium leprae with T cell clones of leprosy patients. Identification of a novel M. This work provides the translational basis for the development of diagnostics, novel host-directed therapies, immune modulatory and antibacterial molecules strategies as well as novel vaccines.
Our clinical research activities focus particularly on 1 host defence against infectious diseases in the immunocompromised host genetic and acquired immunodeficiencies, due to HIV, treatment with biologicals or other immunosuppressants ; 2 on clinical vaccination studies tuberculosis, leprosy, malaria, yellow fever, rabies, Ebola, and vaccination in immunosuppressed individuals ; 3 on antibiotic stewardship in empirical treatment strategies; 4 on experimental human infection models, and 5 on tropical and travel medicine.
In multiple, long-term international collaborations with excellent research institutes in countries where these diseases are endemic, the emergence of non-communicable diseases and their interactions with infectious diseases is also being studied, with a focus on the emerging epidemic of type 2 diabetes. The department has long term expertise in the screening for latent Mycobacterium tuberculosis infection, an important risk factor in the immunocompromised, particularly in those with iatrogenic immunosuppression.
In addition, our vaccination and travel clinic provides optimized vaccination and counselling schemes to such patients with suppressed immunity. Complementary research at the vaccination clinic includes the study of the efficacy of modified active immunisation schedules to induce protective immunity in the immunosuppressed traveller.
The vaccination clinic also explores the efficacy and safety of alternative routes of vaccine administration. Tuberculosis research is a major theme in the research program. Tuberculosis TB is a tremendous global public health problem: over 10 million people develop active TB and 1. The past two centuries over a billion people have died from TB, more than from any other infectious disease. There is no effective vaccine — BCG affords only partial protection and has limited impact on TB transmission, urging for better vaccines.
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Current TB diagnostic tools are insufficient and lack sensitivity and specificity for differential diagnosis of TB, and adequate tools to predict treatment outcome at an early stage are lacking. TB drug resistance is a rapidly increasing problem, calling urgently for novel treatments. Current efforts will fail to achieve the WHO ambition to eliminate this disease before Our TB research responds to these challenges, and is clinical, translational and fundamental in nature and including humanized animal models of TB mice, zebrafish.
Our vaccine program has led to a number of first-in-man clinical studies with newly developed, molecularly defined synthetic TB vaccines. Systems biology, chemical genetics, transcriptomics, metabolomics, lipidomics and immunomics approaches are used to identify the key cellular signalling pathways in host defence to intracellular pathogens in general, and to M. Identified key host regulatory networks and molecules will be used as targets for host-directed therapy to develop alternatives for antibiotic treatment to combat the rise in drug resistant pathogens.
Correlates of protection and prospective correlates of risk of developing TB are being identified. Novel immunological subsets both innate and adaptive have also been identified and provide novel insights which are instrumental for development of novel vaccines and treatment strategies.
Using technologies developed in the TB research program, recent work also enabled identification of biomarkers of Ebola-vaccine induced human responses. 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.
TBRC aims to discover and develop innovative vaccines, biomarkers, diagnostics and therapies for mycobacterial infectious diseases. Leprosy research has been a major research theme at the LUMC since the s.
Recognition of M. leprae antigens | Tom Ottenhoff | Springer
This resulted in the identification of the first HLA-disease associations, the first human helper and regulatory T-cell clones, followed by the identification of M. Besides the M. Collaborations with endemic field sites within the three main continents reporting leprosy are firmly established Brazil, Bangladesh, Ethiopia, Nepal, India exemplified by a large scale BCG vaccination field trial in Bangladesh.
Molecular Cell Biology, user-friendly, field-applicable, first generation lateral flow tests have been developed based on multiple discriminating host biomarkers and the mentioned M. Recent new projects include additional focus on mechanisms of mycobacterial transmission using a One health approach human, animal, environment. Our Department is part of the Leprosy Expertise Center housed at EMC , functions as the national reference centre for routine serological diagnosis of leprosy, and provides this service also to European partners.
In order to focus our research portfolio more on bacterial infectious diseases, this research line is now fully embedded within the Dept of Parasitology LUMC. Research on antimicrobial peptides aims to develop alternatives for antibiotic treatment in the face of the emerging antimicrobial resistance and tolerance. Naturally occurring peptides are selected as lead structures which are further optimized for application and efficacy.
Several human 3-D models, such as skin, airway epithelium and bladder epithelium and animal models 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. The next stage in the antimicrobial peptide research is the development of innovative formulations that promotes the controlled release of the peptide at the site of infection.
A first study with synthetic antimicrobial peptide in patients with chronic suppurative otitis media has been successfully completed Peek et al, Further proof of concept studies in man are being planned for Recently, our Dept. Studies have been initiated in collaboration with the Dept. The projects directly relate to- and are guided by current clinical questions that arise with the emergence of AMR and antifungal resistance.
Empiric and prophylactic treatments in particular are affected in their efficacy by an increasing incidence of AMR, and thus relevant to large groups of patients.