Glycobiology of host-pathogen interaction Group

Glycobiology of helminth infections

Glycans play pivotal roles in the interaction between helminths and their hosts. Applying state-of-the-art glycomics technologies including mass spectrometry and glycan microarrays constructed of native or synthetic glycan antigens we study in detail the glycosylation of schistosomes and other medical or socioeconomically important helminths. By screening antibodies in sera from endemic populations, from infected animals, or from our controlled human infection studies, we identify antigens that are subsequently explored as diagnostic targets in endemic areas, or as glycan-based vaccines in rodent models.

For current, funded translational projects associated with this long-running overall project see Glycan-based diagnostics and biomarkers.

Helminths are masters in modulating the immune response of their host in order to establish long term survival. The immunoregulatory responses that helminths induce have beneficial effects on the development of allergic disorders and type 2 diabetes. In cross-disciplinary studies we identify glycans and glycoconjugates that trigger immunomodulatory mechanisms in in vitro and in vivo models of immunomodulation and immunometabolism. Detailed structure-function studies are supported by using libraries of purified native, (semi-)synthetic and biotechnologically engineered helminth glycoconjugates. These studies in addition contribute to our schistosomiasis and soil-transmitted helminth vaccine development research.

For collaborative intra-departmental  glycobiology research in immunomodulation see also (link to [Hermelijn Smits AWWA], [Bruno  T2D])

Glycan-based diagnostics, biomarkers and anti-glycan antibodies

Based on outcomes of the basic research programs on helminth glycobiology and helminth infections we are highly active in the field of glycan-based diagnostics and biomarkers.

Schistosomes secrete a number of unique glycans and glycoconjugates in the infected host, some of which have formed the basis for successful assays that can detect active schistosome infections. One of these antigens, CAA,  is a unique glycan that can be detected in urine and serum, and it forms the target of antibodies developed at Parasitology and their current application in the development of in a rapid diagnostic test for schistosomiasis. For more information click here.

In addition, research in the group since 2000 has shown that glycan antigens of schistosomes and other helminths give rise to specific anti-glycan antibody signatures in human populations and in animal models for infection and immunity. Using our specialized glycan microarray approaches anti-glycan antibodies are studied at large scale in human cohorts obtained in collaboration with partners in Africa and Asia where helminth infections are endemic, as well as during controlled human infections. The diagnostic potential of these anti-glycan antibodies in schistosomiasis is being explored in a GHIT funded project.

Antigenic and immunogenic glycoproteins

Antigenic and immunogenic glycoproteins

Results from glycomics studies and the identification of glycoprotein antigens of helminths also directly feed into immunological and biological studies of native and recombination glycoproteins as vaccine targets for helminth infections and as immunomodulators of inflammatory conditions. The reconstruction of functional glycosylation of recombinant glycoproteins is not a trivial task as this is dependent on cell- and species-specific glycosylation machineries. Possible solutions are the use of synthetic glycans as explored in collaboration with the Leiden Institute of Chemistry and the use of helminth glycosyltransferase co-expression in a plant production system together with Wageningen University & Research. In a collaborative project funded by the Horizons ICRAD program we are currently testing vaccines against nematodes based on plant-produced glyco-engineered target proteins.