Mimicking immunomodulatory helminth glycoproteins in plants to enable treatment of inflammatory diseases

R.H.P. Wilbers, L.B. Westerhof, Kim van Noort, K. Obieglo, N.N. Driessen, B. Everts, A. Goverse, G. Smant, J. Bakker, H.H. Smits, M. Yazdanbakhsh, A. Schots, C.H. Hokke

Research output: Contribution to conferencePosterAcademic

Abstract

Helminth parasites control host-immune responses by secreting immunomodulatory glycoproteins. Clinical trials and mouse model studies have demonstrated the potential of helminths and 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 helminth glycoproteins. Here we exploited the flexibility of the N-glycosylation machinery of plants to reconstruct two helminth glycoproteins, omega-1 and kappa-5, 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
Publication statusPublished - Feb 2017
EventGlycoBioTec - The Conference Venue of the Max Planck Society, Berlijn, Germany
Duration: 7 Feb 20179 Feb 2017

Conference

ConferenceGlycoBioTec
CountryGermany
CityBerlijn
Period7/02/179/02/17

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