2022, Volume 13, Issue 6
Engineering >> 2022, Volume 13, Issue 6 doi: 10.1016/j.eng.2021.06.012
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
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.
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Abstract
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.
Keywords
Coronavirus ; SARS-CoV-2 ; Vaccine ; Yeast ; Receptor-binding domain (RBD)
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