GM (Geartsje) Bakker

Infections with parasitic worms (helminths) continue to cause a massive global health burden. Yet, effective vaccines to enable control and elimination of helminth infections do not exist. One of the primary reasons is that production platforms tailored to specific helminth vaccine requirements are not available. Vaccine candidates in their native form have glycans that either have reported immunomodulatory activities (e.g. directing specific immune responses and promoting specific receptor-mediated pathways of antigen uptake and processing) or that are direct targets of a (protective) antibody response. Vaccines produced in heterologous expression systems fail to reproduce the specific helminth glycosylation profile, affecting their efficacy. At our laboratory a plant-based expression platform for secreted helminth glycoproteins is under development in which glycans can be engineered in a modular fashion by co-expressing different glycosyltransferases and/or glycosidases alongside the vaccine candidates.

My research focusses on the further development of this plant-based glycoengineering system and using it to produce anthelminthic vaccine antigens. Currently existing and newly discovered vaccine candidates will be tried for expression in our plant system and engineered to contain specific helminth glycosylation profiles. Plant endogenous glycosyltransferases and/or glycosidases can interfere this engineering. Therefore, research will be done on setting up a CRISPR workflow to silence all undesired plant glycosylation enzymes. This will give a better overview of the role of these enzymes in plants, and might lead to the production of effective anthelminthic vaccines that could be used in further vaccine testing.