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莱茵衣藻叶绿体表达一种口服免疫原性蛋白,靶向与动脉粥样硬化免疫治疗相关的 p210 表位。

Chlamydomonas reinhardtii chloroplasts express an orally immunogenic protein targeting the p210 epitope implicated in atherosclerosis immunotherapies.

机构信息

Laboratorio de Biofarmacéuticos Recombinantes, Facultad de Ciencias Químicas, Universidad Autónoma de San Luis Potosí, Av. Dr. Manuel Nava 6, 78210, San Luis, SLP, Mexico.

Laboratorio de Biorreactores, Facultad de Ciencias Químicas, Universidad Autónoma de San Luis Potosí, Av. Dr. Manuel Nava 6, 78210, San Luis, SLP, Mexico.

出版信息

Plant Cell Rep. 2016 May;35(5):1133-41. doi: 10.1007/s00299-016-1946-6. Epub 2016 Feb 17.

Abstract

An algae-based vaccine model against atherosclerosis was developed with positive findings in terms of antigen yield and immunogenicity in mouse. Several immunotherapies against atherosclerosis have been evaluated at the preclinical level thus far, with some of them currently under evaluation in clinical trials. In particular, the p210 epitope from ApoB100 is known to elicit atheroprotective responses. Considering that Chlamydomonas reinhardtii is an attractive host for the production and delivery of subunit vaccines, in this study a chimeric protein consisting of the B subunit of the cholera toxin and the p210 epitope from ApoB100 (CTB:p210) has been expressed in C. reinhardtii chloroplast as an attempt to establish an oral vaccine candidate against atherosclerosis. The Chlamydomonas-made CTB:p210 protein was successfully expressed at levels of up to 60 µg per g of fresh weight biomass. The antigenic activity of the CTB and the p210 moiety was preserved in the CTB:p210 chimera. Moreover the algae-made CTB:p210 showed an immunogenic activity, when orally administered to BALB/c mice, as evidenced the presence of anti-p210 serum antibodies in mice treated with the algae-derived CTB:p210. The antibody response lasts for at least 80 days after the last boost. This experimental model is proposed as a convenient tool in the development of low cost atherosclerosis vaccines of easy compliance and friendly delivery. Further studies will determine the therapeutic potential of this algae-made vaccine in atherosclerosis animal models.

摘要

一种基于藻类的动脉粥样硬化疫苗模型在小鼠中表现出了良好的抗原产量和免疫原性。迄今为止,已有几种针对动脉粥样硬化的免疫疗法在临床前水平进行了评估,其中一些目前正在临床试验中进行评估。特别是 ApoB100 的 p210 表位已被证明可引发动脉粥样硬化保护反应。考虑到莱茵衣藻是生产和递送亚单位疫苗的有吸引力的宿主,本研究在莱茵衣藻叶绿体中表达了由霍乱毒素 B 亚单位和 ApoB100 的 p210 表位组成的嵌合蛋白(CTB:p210),试图建立一种针对动脉粥样硬化的口服疫苗候选物。Chlamydomonas 制造的 CTB:p210 蛋白的表达水平高达每克新鲜重生物质 60μg。CTB 和 p210 部分的抗原活性在 CTB:p210 嵌合体中得以保留。此外,当口服给予 BALB/c 小鼠时,藻类制造的 CTB:p210 表现出免疫原性,用藻类衍生的 CTB:p210 处理的小鼠存在抗 p210 血清抗体证明了这一点。抗体反应在最后一次加强后至少持续 80 天。该实验模型被提议作为开发低成本、易于遵守和友好递送的动脉粥样硬化疫苗的便捷工具。进一步的研究将确定这种藻类疫苗在动脉粥样硬化动物模型中的治疗潜力。

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