A stable platform for the production of virus-like particles pseudotyped with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike protein

被引:17
作者
Roy, Sylvie [1 ]
Ghani, Karim [1 ,2 ]
de Campos-Lima, Pedro O. [3 ,4 ]
Caruso, Manuel [1 ,2 ,5 ]
机构
[1] Univ Laval, CHU Quebec, Res Ctr, Canc Res Ctr,Oncol Div, Quebec City, PQ, Canada
[2] BioVec Pharma, Quebec City, PQ, Canada
[3] Boldrini Childrens Ctr, Campinas, Brazil
[4] Univ Estadual Campinas, Funct & Mol Biol Grad Program, Campinas, Brazil
[5] Univ Laval, Fac Med, Dept Mol Biol Med Biochem & Pathol, Quebec City, PQ, Canada
关键词
COVID-19; Coronavirus; SARS-CoV-2; VLP; Virus-like particle; Retrovirus; Moloney; Vaccine; RETROVIRAL VECTORS; FUNCTIONAL RECEPTOR; S-PROTEIN; VACCINES; ENTRY; GLYCOPROTEIN; SUSPENSION; POTENT; CELLS;
D O I
10.1016/j.virusres.2021.198305
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
In this study, we showed that a codon optimized version of the spike (S) protein of SARS-CoV-2 can migrate to the cell membrane. However, efficient production of Moloney murine leukemia (MLV) infectious viral particles was only achieved with stable expression of a shorter S version in C-terminal (Delta S) in MLV Gag-pol expressing cells. As compared to transient transfections, this platform generated viruses with a 1000-fold higher titer. Delta S was 15-times more efficiently incorporated into VLPs as compared to S, and that was not due to steric inter-ference between the cytoplasmic tail and the MLV capsid, as similar differences were also observed with extracellular vesicles. The amount of Delta S incorporated into VLPs released from producer cells was high and estimated at 1.25 mu g/mL S2 equivalent (S is comprised of S1 and S2). The resulting VLPs could potentially be used alone or as a boost of other immunization strategies for COVID-19.
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页数:10
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