Transgenic plants expressing autoantigens fed to mice to induce oral immune tolerance

Abstract

Oral administration of protein can induce antigen-specific immune hyporesponsiveness. However, the utility of oral tolerance to autoantigens in the treatment of autoimmune diseases may be limited when candidate autoantigens cannot be produced by conventional systems in quantities sufficient for clinical studies. Plants may be ideally suited for this purpose, as they can synthesize, glycosylate and assemble mammalian proteins to provide huge quantities of relatively low cost soluble proteins. Furthermore, edible transgenic plants could provide a simple and direct method of autoantigen delivery for oral tolerance. Therefore, the aim of this study was to determine whether a transgenic plant expression system was capable of synthesizing the diabetes-associated autoantigen, glutamic acid decarboxylase (GAD) in an immunogenic form and whether the oral administration of an autoantigen expressed by a plant could directly induce protective immune responses in a mouse model of diabetes. We show that a GAD-expressing transgenic plant, given as a dietary supplement, inhibits the development of diabetes in the non-obese diabetic (NOD) mouse.

Prevention of autoimmune diabetes by immunogene therapy using recombinant vaccinia virus expressing glutamic acid decarboxylase

“…We found that the production of IL-4 increased, whereas the production of IFN-γ decreased, indicating that the immunisation of NOD mice with rVV-GAD65 induced a Th2 immune response in an antigenspecific manner. Our finding is consistent with the results of previous reports on NOD mice treated with GAD protein systemically, nasally or orally [28,29,33,34,35] or vaccinated with GAD encoding plasmid DNA [41]. Th2 immune responses induced by rVV-GAD immunisation could play an important role in the prevention of autoimmune diabetes in this animal model.…”

“…In Type I diabetes, GAD and insulin have been identified as major autoantigens and tolerisation against these autoantigens has been attempted as a method for the prevention of the disease [14,32]. It has been reported that administration of purified GAD protein or peptide or insulin protein or peptide to NOD mice by a variety of routes can tolerise the T cell-mediated immune response against pancreatic beta cells, resulting in the prevention or delay of the development of insulitis and diabetes [28,29,33,34,35,36,37,38,39]. In many cases, the preventive effect was found to be associated with a Th2 shift [14,32].…”

Construction of a Der p2-transgenic plant for the alleviation of airway inflammation

“…The ratio of target protein to total protein in our system was higher than that obtained from a previous study. 17 In this study, we chose the clone with the highest Der p2 expression level (Der p2 expressed in the cytosol) for the protein extraction. The amount of Der p2 from a total protein extraction of 35 g dry weight callus can be up to 0.185 g. The Der p2 expression in transgenic tobacco plant cells is shown in Figure 1c.…”

“…In addition, the exceptional stability of transgenic proteins allows for ease of storage and transportation. 17 Additionally, using plants to express recombinant proteins prevents production of unwanted byproducts such as endotoxin production, which can be produced from Escherichia coli expression systems.…”

Stiff-man syndrome: From the bedside to the bench

“…Recently, a transgenic plant capable of synthesizing GAD in an immunogenic form has been described (91). One may speculate whether the oral administration of the putative autoantigen of SMS can induce protective immune responses in patients with SMS.…”