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《工程(英文)》 >> 2022年 第13卷 第6期 doi: 10.1016/j.eng.2021.06.012

糖基工程毕赤酵母制备的SARS-CoV-2 S蛋白RBD受体结合区亚单位疫苗可激发中和抗体反应

a Department of Microorganism Engineering, Beijing Institute of Biotechnology, Beijing 100071, China
b Medical Innovation Research Division & Fourth Medical Center of the Chinese PLA General Hospital, Beijing 100853, China
c Department of Neurosurgery, First Medical Center of the Chinese PLA General Hospital, Beijing 100853, China
d Shenzhen Taihe Biotechnology Co. Ltd., Shenzhen 518001, China
e Institute of Physical Science and Information Technology, Anhui University, Hefei 230000, China

# These authors contributed equally to this work.

收稿日期: 2021-02-04 修回日期: 2021-05-05 录用日期: 2021-06-11 发布日期: 2021-07-13

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摘要

2020年至今,新型冠状病毒SARS-CoV-2已经在全球大流行。新冠疫苗被寄于厚望用以减轻防控压力,成为解决疫情危机的有效手段之一。SARS-CoV-2通过S蛋白受体结合区RBD与宿主细胞ACE2受体结合侵染机体。本文提供了一种利用新型糖基工程毕赤酵母表达系统,制备基于S蛋白RBD重组亚单位候选疫苗的方法。该糖基工程酵母的糖基化修饰途径经过人源化改造后,具有类似于哺乳动物细胞糖基化修饰特点。研究发现,RBD候选疫苗可以有效地诱导小鼠产生高滴度的抗RBD特异性抗体,含Al(OH)3和CpG双佐剂的RBD免疫组小鼠产生的特异性抗体滴度和病毒中和抗体滴度显著地高于Al(OH)3单佐剂组,且中和抗体可以在小鼠体内持续6个月以上。综上所述,本文利用糖基工程酵母制备了SARS-CoV-2 S蛋白RBD糖蛋白疫苗,该疫苗能够诱导小鼠产生高滴度中和抗体,同时提供了一种可制备具有无岩藻糖的复杂型N-糖基化修饰重组蛋白的方法。

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