A Vaccine Based on the Receptor-Binding Domain of the Spike Protein Expressed in Glycoengineered Pichia pastoris Targeting SARS-CoV-2 Stimulates Neutralizing and Protective Antibody Responses

作     者：Bo Liu Ying Yin Yuxiao Liu Tiantian Wang Peng Sun Yangqin Ou Xin Gong Xuchen Hou Jun Zhang Hongguang Ren Shiqiang Luo Qian Ke Yongming Yao Junjie Xu Jun Wu Bo Liu;Ying Yin;Yuxiao Liu;Tiantian Wang;Peng Sun;Yangqin Ou;Xin Gong;Xuchen Hou;Jun Zhang;Hongguang Ren;Shiqiang Luo;Qian Ke;Yongming Yao;Junjie Xu;Jun Wu

作者机构：Department of Microorganism EngineeringBeijing Institute of BiotechnologyBeijing 100071China Medical Innovation Research Division&Fourth Medical Center of the Chinese PLA General HospitalBeijing 100853China Department of NeurosurgeryFirst Medical Center of the Chinese PLA General HospitalBeijing 100853China Shenzhen Taihe Biotechnology Co.Ltd.Shenzhen 518001China Institute of Physical Science and Information TechnologyAnhui UniversityHefei 230000China 

出 版 物：《Engineering》 (工程（英文）)

年 卷 期：2022年第8卷第6期

页      面：107-115页

核心收录：

学科分类：0710[理学-生物学] 1007[医学-药学(可授医学、理学学位)] 0832[工学-食品科学与工程（可授工学、农学学位）] 100705[医学-微生物与生化药学] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 0805[工学-材料科学与工程（可授工学、理学学位）] 10[医学] 

基　　金：supported by the National Key Research and Development Program of China (2020YFC0841400-008) the National Science and Technology Major Projects(2018ZX09711003-013-002) the National Natural Science Foundation of China (81673339 and 81773619) 

主　　题：Coronavirus SARS-CoV-2 Vaccine Yeast Receptor-binding domain(RBD) 

摘      要：In 2020 and 2021,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),a novel coronavirus,caused a global pandemic.Vaccines are expected to reduce the pressure of prevention and control,and have become the most effective strategy to solve the pandemic crisis.SARS-CoV-2 infects the host by binding to the cellular receptor angiotensin converting enzyme 2(ACE2)via the receptor-binding domain(RBD)of the surface spike(S)glycoprotein.In this study,a candidate vaccine based on a RBD recombinant subunit was prepared by means of a novel glycoengineered yeast Pichia pastoris expression system with characteristics of glycosylation modification similar to those of mammalian cells.The candidate vaccine effectively stimulated mice to produce high-titer anti-RBD specific antibody.Furthermore,the specific antibody titer and virus-neutralizing antibody(NAb)titer induced by the vaccine were increased significantly by the combination of the double adjuvants Al(OH)_(3) and CpG.Our results showed that the virus-NAb lasted for more than six months in mice.To summarize,we have obtained a SARS-CoV-2 vaccine based on the RBD of the S glycoprotein expressed in glycoengineered Pichia pastoris,which stimulates neutralizing and protective antibody responses.A technical route for fucose-free complex-type N-glycosylation modified recombinant subunit vaccine preparation has been established.