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
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
Affiliations
Bo Liu
Department of Microorganism Engineering, Beijing Institute of Biotechnology, Beijing 100071, China
Ying Yin
Department of Microorganism Engineering, Beijing Institute of Biotechnology, Beijing 100071, China
Yuxiao Liu
Medical Innovation Research Division & Fourth Medical Center of the Chinese PLA General Hospital, Beijing 100853, China; Department of Neurosurgery, First Medical Center of the Chinese PLA General Hospital, Beijing 100853, China
Tiantian Wang
Department of Microorganism Engineering, Beijing Institute of Biotechnology, Beijing 100071, China
Peng Sun
Department of Microorganism Engineering, Beijing Institute of Biotechnology, Beijing 100071, China
Yangqin Ou
Shenzhen Taihe Biotechnology Co. Ltd., Shenzhen 518001, China
Xin Gong
Department of Microorganism Engineering, Beijing Institute of Biotechnology, Beijing 100071, China
Xuchen Hou
Department of Microorganism Engineering, Beijing Institute of Biotechnology, Beijing 100071, China
Jun Zhang
Department of Microorganism Engineering, Beijing Institute of Biotechnology, Beijing 100071, China
Hongguang Ren
Department of Microorganism Engineering, Beijing Institute of Biotechnology, Beijing 100071, China
Shiqiang Luo
Department of Microorganism Engineering, Beijing Institute of Biotechnology, Beijing 100071, China; Institute of Physical Science and Information Technology, Anhui University, Hefei 230000, China
Qian Ke
Department of Microorganism Engineering, Beijing Institute of Biotechnology, Beijing 100071, China; Institute of Physical Science and Information Technology, Anhui University, Hefei 230000, China
Yongming Yao
Medical Innovation Research Division & Fourth Medical Center of the Chinese PLA General Hospital, Beijing 100853, China; Corresponding authors.
Junjie Xu
Department of Microorganism Engineering, Beijing Institute of Biotechnology, Beijing 100071, China; Corresponding authors.
Jun Wu
Department of Microorganism Engineering, Beijing Institute of Biotechnology, Beijing 100071, China; Corresponding authors.
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.
