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

Fingerprint

Helminths
Glycoproteins
Glycosylation
Parasites
Communicable Disease Control
Antigens
Glycosyltransferases
Schistosoma mansoni
Immune System Diseases
Recombinant Proteins
Autoimmune Diseases
Tobacco
Polysaccharides
Ovum
Hypersensitivity
Vaccines
Carbohydrates
Clinical Trials
Proteins

Cite this

Wilbers, R. H. P., Westerhof, L. B., van Noort, K., Obieglo, K., Driessen, N. N., Everts, B., ... Hokke, C. H. (2017). Mimicking immunomodulatory helminth glycoproteins in plants to enable treatment of inflammatory diseases. Poster session presented at GlycoBioTec, Berlijn, Germany.
Wilbers, R.H.P. ; Westerhof, L.B. ; van Noort, Kim ; Obieglo, K. ; Driessen, N.N. ; Everts, B. ; Goverse, A. ; Smant, G. ; Bakker, J. ; Smits, H.H. ; Yazdanbakhsh, M. ; Schots, A. ; Hokke, C.H. / Mimicking immunomodulatory helminth glycoproteins in plants to enable treatment of inflammatory diseases. Poster session presented at GlycoBioTec, Berlijn, Germany.
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title = "Mimicking immunomodulatory helminth glycoproteins in plants to enable treatment of inflammatory diseases",
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.",
author = "R.H.P. Wilbers and L.B. Westerhof and {van Noort}, Kim and K. Obieglo and N.N. Driessen and B. Everts and A. Goverse and G. Smant and J. Bakker and H.H. Smits and M. Yazdanbakhsh and A. Schots and C.H. Hokke",
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language = "English",
note = "GlycoBioTec ; Conference date: 07-02-2017 Through 09-02-2017",

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Wilbers, RHP, Westerhof, LB, van Noort, K, Obieglo, K, Driessen, NN, Everts, B, Goverse, A, Smant, G, Bakker, J, Smits, HH, Yazdanbakhsh, M, Schots, A & Hokke, CH 2017, 'Mimicking immunomodulatory helminth glycoproteins in plants to enable treatment of inflammatory diseases' GlycoBioTec, Berlijn, Germany, 7/02/17 - 9/02/17, .

Mimicking immunomodulatory helminth glycoproteins in plants to enable treatment of inflammatory diseases. / Wilbers, R.H.P.; Westerhof, L.B.; van Noort, Kim; Obieglo, K.; Driessen, N.N.; Everts, B.; Goverse, A.; Smant, G.; Bakker, J.; Smits, H.H.; Yazdanbakhsh, M.; Schots, A.; Hokke, C.H.

2017. Poster session presented at GlycoBioTec, Berlijn, Germany.

Research output: Contribution to conferencePosterAcademic

TY - CONF

T1 - Mimicking immunomodulatory helminth glycoproteins in plants to enable treatment of inflammatory diseases

AU - Wilbers, R.H.P.

AU - Westerhof, L.B.

AU - van Noort, Kim

AU - Obieglo, K.

AU - Driessen, N.N.

AU - Everts, B.

AU - Goverse, A.

AU - Smant, G.

AU - Bakker, J.

AU - Smits, H.H.

AU - Yazdanbakhsh, M.

AU - Schots, A.

AU - Hokke, C.H.

PY - 2017/2

Y1 - 2017/2

N2 - 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.

AB - 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.

M3 - Poster

ER -

Wilbers RHP, Westerhof LB, van Noort K, Obieglo K, Driessen NN, Everts B et al. Mimicking immunomodulatory helminth glycoproteins in plants to enable treatment of inflammatory diseases. 2017. Poster session presented at GlycoBioTec, Berlijn, Germany.