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用于治疗日本雪松和柏树花粉过敏的水稻基肽疫苗的研发。

Development of a rice-based peptide vaccine for Japanese cedar and cypress pollen allergies.

作者信息

Takaiwa Fumio, Yang Lijun

机构信息

Functional Transgenic Crop Research Unit, National Institute of Agrobiological Sciences, Kannondai 2-1-2, Tsukuba, Ibaraki, 305-8602, Japan,

出版信息

Transgenic Res. 2014 Aug;23(4):573-84. doi: 10.1007/s11248-014-9790-3. Epub 2014 Mar 18.

DOI:10.1007/s11248-014-9790-3
PMID:24638148
Abstract

Peptide immunotherapy using dominant T-cell epitopes is a safe treatment alternative to conventional subcutaneous injection of natural crude allergen extract, which is sometimes accompanied by anaphylactic shock. For Japanese cedar pollinosis (JCP), hybrid peptides composed of six to seven major T-cell epitopes (7Crp peptide) from the causative allergens Cry j 1 and Cry j 2 have been developed on the basis of different human leukemia antigen class II restrictions, because of the diversity of patients' genetic backgrounds. However, other dominant T-cell epitopes that are produced in some patients are not covered by these peptides. To develop a more universal peptide vaccine for JCP, we generated transgenic rice seeds containing seven new T-cell epitopes (Crp3) in addition to the T-cell epitopes used in the 7Crp peptide. Next, we co-expressed unique T-cell epitopes (6Chao) from the Japanese cypress pollen allergens Cha o 1 and Cha o 2 in transgenic rice seeds, with 7Crp and Crp3. These transgenic rice seeds, containing many highly homologous T-cell epitopes derived from cedar and cypress allergens, are expected to be applicable to a wide range of patients suffering from these pollen allergies.

摘要

使用显性T细胞表位的肽免疫疗法是一种安全的治疗选择,可替代传统的皮下注射天然粗制过敏原提取物,后者有时会伴随过敏性休克。对于日本雪松花粉症(JCP),由于患者遗传背景的多样性,基于不同的人类白血病抗原II类限制,已开发出由来自致病过敏原Cry j 1和Cry j 2的六至七个主要T细胞表位组成的杂合肽(7Crp肽)。然而, 一些患者产生的其他显性T细胞表位并未被这些肽所覆盖。为了开发一种更通用的JCP肽疫苗,我们培育出了转基因水稻种子,其中除了含有7Crp肽中使用的T细胞表位外,还含有七个新的T细胞表位(Crp3)。接下来,我们在转基因水稻种子中,将来自日本扁柏花粉过敏原Cha o 1和Cha o 2的独特T细胞表位(6Chao)与7Crp和Crp3共表达。这些转基因水稻种子含有许多源自雪松和扁柏过敏原的高度同源T细胞表位,有望适用于广泛的这些花粉过敏患者。

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Development of a rice-based peptide vaccine for Japanese cedar and cypress pollen allergies.用于治疗日本雪松和柏树花粉过敏的水稻基肽疫苗的研发。
Transgenic Res. 2014 Aug;23(4):573-84. doi: 10.1007/s11248-014-9790-3. Epub 2014 Mar 18.
2
Immunological and Symptomatic Effects of Oral Intake of Transgenic Rice Containing 7 Linked Major T-Cell Epitopes from Japanese Cedar Pollen Allergens.口服含有来自日本扁柏花粉过敏原的 7 个串联主要 T 细胞表位的转基因大米的免疫和症状效应。
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Recognition of T cell epitopes unique to Cha o 2, the major allergen in Japanese cypress pollen, in allergic patients cross-reactive to Japanese cedar and Japanese cypress pollen.在对日本柳杉花粉和日本扁柏花粉交叉反应的过敏患者中识别日本扁柏花粉主要过敏原Cha o 2特有的T细胞表位。
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Identification of human T cell epitopes in Japanese cypress pollen allergen, Cha o 1, elucidates the intrinsic mechanism of cross-allergenicity between Cha o 1 and Cry j 1, the major allergen of Japanese cedar pollen, at the T cell level.日本扁柏花粉过敏原Cha o 1中人类T细胞表位的鉴定,阐明了Cha o 1与日本柳杉花粉主要过敏原Cry j 1在T细胞水平上交叉致敏性的内在机制。
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Long-term oral administration of transgenic rice containing cedar pollen T-cell epitopes potentially improves medication- and allergy-related quality-of-life scores.长期口服含有雪松花粉 T 细胞表位的转基因水稻可能改善与药物和过敏相关的生活质量评分。
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Immunotargets Ther. 2021 Jul 2;10:213-224. doi: 10.2147/ITT.S276874. eCollection 2021.
2
Solid-in-Oil Nanodispersions for Transcutaneous Immunotherapy of Japanese Cedar Pollinosis.用于日本雪松花粉症经皮免疫治疗的油包固纳米分散体
Pharmaceutics. 2020 Mar 7;12(3):240. doi: 10.3390/pharmaceutics12030240.
3
Transcutaneous pollinosis immunotherapy using a solid-in-oil nanodispersion system carrying T cell epitope peptide and R848.

本文引用的文献

1
The use of rice seeds to produce human pharmaceuticals for oral therapy.利用水稻种子生产用于口服治疗的人类药物。
Biotechnol J. 2013 Oct;8(10):1133-43. doi: 10.1002/biot.201300065. Epub 2013 Sep 17.
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Update on the use of transgenic rice seeds in oral immunotherapy.转基因水稻种子在口服免疫治疗中的应用进展。
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Recombinant protein yield in rice seed is enhanced by specific suppression of endogenous seed proteins at the same deposit site.通过在同一储存位点特异性抑制内源种子蛋白,可提高水稻种子中重组蛋白的产量。
使用携带T细胞表位肽和R848的油包固纳米分散系统进行经皮花粉症免疫疗法。
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Production of BP178, a derivative of the synthetic antibacterial peptide BP100, in the rice seed endosperm.在水稻种子胚乳中合成抗菌肽BP100的衍生物BP178。
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Molecular Breeding to Create Optimized Crops: From Genetic Manipulation to Potential Applications in Plant Factories.通过分子育种培育优化作物:从基因操纵到在植物工厂中的潜在应用
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Seed-based oral vaccines as allergen-specific immunotherapies.基于种子的口服疫苗作为变应原特异性免疫疗法。
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Rice seed ER-derived protein body as an efficient delivery vehicle for oral tolerogenic peptides.水稻种子 ER 衍生蛋白体作为口服免疫耐受肽的有效传递载体。
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Annu Rev Immunol. 2010;28:211-41. doi: 10.1146/annurev-immunol-030409-101218.
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Allergen immunotherapy.变应原免疫治疗。
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Induction of IL-10-producing regulatory T cells with TCR diversity by epitope-specific immunotherapy in pollinosis.在花粉症中通过表位特异性免疫疗法诱导具有TCR多样性的产生白细胞介素-10的调节性T细胞
J Allergy Clin Immunol. 2009 Oct;124(4):842-5.e7. doi: 10.1016/j.jaci.2009.06.020. Epub 2009 Aug 22.
9
Recognition of T cell epitopes unique to Cha o 2, the major allergen in Japanese cypress pollen, in allergic patients cross-reactive to Japanese cedar and Japanese cypress pollen.在对日本柳杉花粉和日本扁柏花粉交叉反应的过敏患者中识别日本扁柏花粉主要过敏原Cha o 2特有的T细胞表位。
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Deposition of a recombinant peptide in ER-derived protein bodies by retention with cysteine-rich prolamins in transgenic rice seed.通过在转基因水稻种子中与富含半胱氨酸的醇溶蛋白保留结合,将重组肽沉积在内质网衍生的蛋白体中。
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