Production and glyco-engineering of immunomodulatory helminth glycoproteins in plants

Ruud H.P. Wilbers*, Lotte B. Westerhof, Kim Van Noort, Katja Obieglo, Nicole N. Driessen, Bart Everts, Sonja I. Gringhuis, Gabriele Schramm, Aska Goverse, Geert Smant, Jaap Bakker, Hermelijn H. Smits, Maria Yazdanbakhsh, Arjen Schots, Cornelis H. Hokke

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

22 Citations (Scopus)

Abstract

Helminth parasites control host-immune responses by secreting immunomodulatory glycoproteins. Clinical trials and mouse model studies have demonstrated the potential of helminth-derived glycoproteins for the treatment of immune-related diseases, like allergies and autoimmune diseases. Studies are however hampered by the limited availability of native parasite-derived proteins. Moreover, recombinant protein production systems have thus far been unable to reconstitute helminth-like glycosylation essential for the functionality of some helminth glycoproteins. Here we exploited the flexibility of the N-glycosylation machinery of plants to reconstruct the helminth glycoproteins omega-1 and kappa-5, two major constituents of immunomodulatory Schistosoma mansoni soluble egg antigens. Fine-tuning transient co-expression of specific glycosyltransferases in Nicotiana benthamiana enabled the synthesis of Lewis X (LeX) and LDN/LDN-F glycan motifs as found on natural omega-1 and kappa-5, respectively. In vitro and in vivo evaluation of the introduction of native LeX motifs on plant-produced omega-1 confirmed that LeX on omega-1 contributes to the glycoprotein’s Th2-inducing properties. These data indicate that mimicking the complex carbohydrate structures of helminths in plants is a promising strategy to allow targeted evaluation of therapeutic glycoproteins for the treatment of inflammatory disorders. In addition, our results offer perspectives for the development of effective anti-helminthic vaccines by reconstructing native parasite glycoprotein antigens.
Original languageEnglish
Article number45910
JournalScientific Reports
Volume7
DOIs
Publication statusPublished - 2017

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    Wilbers, R. H. P., Westerhof, L. B., Van Noort, K., Obieglo, K., Driessen, N. N., Everts, B., Gringhuis, S. I., Schramm, G., Goverse, A., Smant, G., Bakker, J., Smits, H. H., Yazdanbakhsh, M., Schots, A., & Hokke, C. H. (2017). Production and glyco-engineering of immunomodulatory helminth glycoproteins in plants. Scientific Reports, 7, [45910]. https://doi.org/10.1038/srep45910