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利用Algevir系统在裂殖壶菌微藻中高效表达一种阿尔茨海默病候选疫苗

Efficient Expression of an Alzheimer's Disease Vaccine Candidate in the Microalga Schizochytrium sp. Using the Algevir System.

作者信息

Ortega-Berlanga Benita, Bañuelos-Hernández Bernardo, Rosales-Mendoza Sergio

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 Potosí, SLP, Mexico.

Sección de Biotecnología, Centro de Investigación en Ciencias de la Salud y Biomedicina, Universidad Autónoma de San Luis Potosí, Av. Dr. Manuel Nava 6, 78210, San Luis Potosí, SLP, Mexico.

出版信息

Mol Biotechnol. 2018 May;60(5):362-368. doi: 10.1007/s12033-018-0077-4.

Abstract

Alzheimer's disease (AD) is the most common neurodegenerative disease, where β-amyloid (Aβ) plays a key role in forming conglomerated senile plaques. The receptor of advanced glycation end products (RAGE) is considered a therapeutic target since it transports Aβ into the central nervous system, favoring the pathology progression. Due to the lack of effective therapies for AD, several therapeutic approaches are under development, being vaccines considered a promising alternative. Herein, the use of the Algevir system was explored to produce in the Schizochytrium sp. microalga the LTB:RAGE vaccine candidate. Algevir relies in an inducible geminiviral vector and led to yields of up to 380 µg LTB:RAGE/g fresh weight biomass at 48-h post-induction. The Schizochytrium-produced LTB:RAGE vaccine retained its antigenic activity and was highly stable up to temperatures of 60 °C. These data demonstrate the potential of Schizochytrium sp. as a platform for high production of thermostable recombinant antigens useful for vaccination against AD.

摘要

阿尔茨海默病(AD)是最常见的神经退行性疾病,其中β-淀粉样蛋白(Aβ)在形成聚集的老年斑中起关键作用。晚期糖基化终产物受体(RAGE)被认为是一个治疗靶点,因为它将Aβ转运到中枢神经系统,促进病理进展。由于缺乏针对AD的有效疗法,几种治疗方法正在研发中,疫苗被认为是一种有前景的替代方案。在此,探索了使用Algevir系统在裂殖壶菌属微藻中生产LTB:RAGE疫苗候选物。Algevir依赖于一种可诱导的双生病毒载体,诱导后48小时在裂殖壶菌中LTB:RAGE的产量高达380μg/g鲜重生物量。裂殖壶菌生产的LTB:RAGE疫苗保留了其抗原活性,在高达60°C的温度下高度稳定。这些数据证明了裂殖壶菌属作为一个平台用于高产热稳定重组抗原以用于AD疫苗接种的潜力。

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