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Production and glyco-engineering of immunomodulatory helminth glycoproteins in plants
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Production and glyco-engineering of immunomodulatory helminth glycoproteins in plants
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Journal Article
Production and glyco-engineering of immunomodulatory helminth glycoproteins in plants
2017
Overview
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.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 13/106
/ 13/21
/ 38/77
/ 42/44
/ 64/60
/ 82/80
/ 82/83
/ Animals
/ Antibodies, Helminth - genetics
/ Antibodies, Helminth - immunology
/ Antibodies, Helminth - metabolism
/ Antigens
/ Antigens, Helminth - genetics
/ Antigens, Helminth - immunology
/ Antigens, Helminth - metabolism
/ EPS
/ Gene Expression - immunology
/ Helminth Proteins - genetics
/ Helminth Proteins - immunology
/ Helminth Proteins - metabolism
/ Humanities and Social Sciences
/ Immunomodulation - immunology
/ Laboratorium voor Nematologie
/ Mimicry
/ PE&RC
/ Recombinant Proteins - immunology
/ Recombinant Proteins - metabolism
/ Schistosoma mansoni - genetics
/ Schistosoma mansoni - immunology
/ Schistosoma mansoni - metabolism
/ Science
