Prevention of allergic conjunctivitis in mice by a rice-based edible vaccine containing modified Japanese cedar pollen allergens

Fukuda, Ken; Ishida, Waka; Harada, Yosuke; Wakasa, Yuhya; Takagi, Hidenori; Takaiwa, Fumio; Fukushima, Atsuki

doi:10.1136/bjophthalmol-2014-305842

Cited by 21 publications

(20 citation statements)

References 15 publications

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“…An example of an early proof of concept for PMF is the production of plant-derived edible human vaccines, using leafy plants or fruits [ 30 , 31 , 32 , 33 , 34 , 35 ]. Edible vaccines are an ideal product in concept since the vaccine could be administered to people orally, theoretically without the need of professional health care workers or sterile injections.…”

Section: Introductionmentioning

confidence: 99%

Plants as Factories for Human Pharmaceuticals: Applications and Challenges

Yao

Weng

Dickey

et al. 2015

IJMS

224

162

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Plant molecular farming (PMF), defined as the practice of using plants to produce human therapeutic proteins, has received worldwide interest. PMF has grown and advanced considerably over the past two decades. A number of therapeutic proteins have been produced in plants, some of which have been through pre-clinical or clinical trials and are close to commercialization. Plants have the potential to mass-produce pharmaceutical products with less cost than traditional methods. Tobacco-derived antibodies have been tested and used to combat the Ebola outbreak in Africa. Genetically engineered immunoadhesin (DPP4-Fc) produced in green plants has been shown to be able to bind to MERS-CoV (Middle East Respiratory Syndrome), preventing the virus from infecting lung cells. Biosafety concerns (such as pollen contamination and immunogenicity of plant-specific glycans) and costly downstream extraction and purification requirements, however, have hampered PMF production from moving from the laboratory to industrial application. In this review, the challenges and opportunities of PMF are discussed. Topics addressed include; transformation and expression systems, plant bioreactors, safety concerns, and various opportunities to produce topical applications and health supplements.

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Section: Introductionmentioning

confidence: 99%

Plants as Factories for Human Pharmaceuticals: Applications and Challenges

Yao

Weng

Dickey

et al. 2015

IJMS

224

162

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“…However, our novel platform has several advantages. First, the magnICON ® system produces the recombinant protein in a much shorter timeframe (up to 2 weeks) compared to transgenic or transplastomic lettuce, rice, carrots and maize ( Uvarova et al, 2013 ; Fukuda et al, 2015 ; Nahampun et al, 2015 ; Su et al, 2015 ). Second, the magnICON ® system achieves higher yields than other transient expression systems in edible species ( Clarke et al, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2018

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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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“…3 Recently, transgenic rice seeds that contain genetically modified Cry j 1 and Cry j 2, the two major allergens of C. japonica (JC), have been developed as immunotherapeutic candidates for JC pollinosis. Although the efficacy of oral immunotherapy with TG-rice seeds has already been demonstrated in mouse models, [9][10][11] it is unknown whether Cry j 1 and Cry j 2 antigenicity is completely preserved in TG-rice seeds. 4 The transgenic rice (TG-rice) seeds express allergens containing whole amino acid sequences of Cry j 1 and Cry j 2 in the endosperm tissue (edible part of rice grain): Cry j 1 gene was divided into three overlapping fragments, and the amino acid sequence of Cry j 2 gene was shuffled.…”

Section: Introductionmentioning

confidence: 99%

“…8 Because TG-rice seeds contain whole amino acid sequences of Cry j 1 and Cry j 2, it is possible that all types of Cry j 1-or Cry j 2-specific T-cells could be targeted. Although the efficacy of oral immunotherapy with TG-rice seeds has already been demonstrated in mouse models, [9][10][11] it is unknown whether Cry j 1 and Cry j 2 antigenicity is completely preserved in TG-rice seeds. Accordingly, the aim of this study was to prove the antigenicity of TG-rice seeds to Cry j 1-or Cry j 2-specific T-cells by analysing the proliferative responses of T-cells in Cry j 1-or Cry j 2-immunized mice or established T-cell lines to TG-rice seed extract.…”

Section: Introductionmentioning

confidence: 99%

T‐cell activation by transgenic rice seeds expressing the genetically modified Japanese cedar pollen allergens

et al. 2019

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Summary Transgenic rice seeds that contain genetically modified Cry j 1 and Cry j 2, the two major allergens of Cryptomeria japonica (Japanese cedar; JC), have been developed as immunotherapeutic candidates for JC pollinosis. Because the transgenic rice (TG‐rice) seeds express allergens containing whole amino acid sequences of Cry j 1 and Cry j 2 in the endosperm tissue (edible part of rice grain), they can potentially target all Cry j 1‐ and Cry j 2‐specific T‐cells. However, it was unknown whether antigenicity of Cry j 1 and Cry j 2 could be completely preserved in TG‐rice seeds. We verified the antigenicity of TG‐rice seeds to T‐cells through the analysis of the proliferative responses of T‐cells in Cry j 1‐ or Cry j 2‐immunized mice or T‐cell lines to TG‐rice seed extract. First, four mouse strains were immunized with Cry j 1 or Cry j 2. T‐cells in the immunized mice proliferated on treatment with TG‐rice seed extract, but not non‐transgenic wild‐type rice (WT‐rice) seed extract. Furthermore, T‐cell lines were established from the spleen cells of the immunized mice. Each T‐cell line resulted in a proliferative response to TG‐rice seed extract, but not to WT‐rice seed extract, suggesting that TG‐rice seeds certainly express T‐cell epitopes corresponding to T‐cell lines. Considering the modified amino acid sequences of Cry j 1 and Cry j 2 in TG‐rice seeds, the expression of specific T‐cell epitopes suggested that TG‐rice seeds express all possible T‐cell epitope repertoires of Cry j 1 and Cry j 2.

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Prevention of allergic conjunctivitis in mice by a rice-based edible vaccine containing modified Japanese cedar pollen allergens

Cited by 21 publications

References 15 publications

Plants as Factories for Human Pharmaceuticals: Applications and Challenges

Plants as Factories for Human Pharmaceuticals: Applications and Challenges

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

T‐cell activation by transgenic rice seeds expressing the genetically modified Japanese cedar pollen allergens

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