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  • Design of a Type-1 Diabetes Vaccine Candidate Using Edible Plants Expressing a Major Autoantigen.

Design of a Type-1 Diabetes Vaccine Candidate Using Edible Plants Expressing a Major Autoantigen.

Frontiers in plant science (2018-05-17)
Edoardo Bertini, Matilde Merlin, Elisa Gecchele, Andrea Puggia, Annalisa Brozzetti, Mauro Commisso, Alberto Falorni, Vittorio Bini, Victor Klymyuk, Mario Pezzotti, Linda Avesani
摘要

Type-1 diabetes (T1D) is a metabolic disease involving the autoimmune destruction of insulin-producing pancreatic beta cells. It is often diagnosed by the detection of autoantibodies, typically those recognizing insulin itself or the 65-kDa isoform of glutamic acid decarboxylase (GAD65). Oral insulin can be used to induce systemic immunological tolerance and thus prevent or delay the onset of T1D, suggesting that combination treatments with other autoantigens such as GAD65 could be even more successful. GAD65 has induced oral tolerance and prevented T1D in preclinical studies but it is difficult to produce in sufficient quantities for clinical testing. Here we combined edible plant systems, namely spinach (Spinacia oleracea cv Industra) and red beet (Beta vulgaris cv Moulin Rouge), with the magnICON® expression system to develop a safe, cost-effective and environmentally sustainable platform for the large-scale production of GAD65. The superior red beet platform was extensively characterized in terms of recombinant protein yields and bioequivalence to wild-type plants, and the product was tested for its ability to resist simulated gastric digestion. Our results indicate that red beet plants are suitable for the production of a candidate oral vaccine based on GAD65 for the future preclinical and clinical testing of T1D immunotherapy approaches.

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Sigma-Aldrich
胃蛋白酶 来源于猪胃粘膜, lyophilized powder, ≥2,500 units/mg protein (E1%/280)
Sigma-Aldrich
抗-兔IgG(全分子)-过氧化物酶 山羊抗, affinity isolated antibody, buffered aqueous solution
Sigma-Aldrich
抗谷氨酸脱羧酶 65/67 兔抗, IgG fraction of antiserum, buffered aqueous solution