Abstract
An array of SARS-CoV-2 virus variants have been isolated, propagated and used in in vitro assays, in vivo animal studies and human clinical trials. Observations of working stocks of SARS-CoV-2 suggest that sequential propagation in Vero cells leads to critical changes in the region of the furin cleavage site, which significantly reduce the value of the working stock for critical research studies. Serially propagating SARS-CoV-2 in Vero E6 cells leads to rapid increases in genetic variants while propagation in other cell lines (e.g. Vero/hSLAM) appears to mitigate this risk thereby improving the overall genetic stability of working stocks. From these observations, investigators are urged to monitor genetic variants carefully when propagating SARS-CoV-2 in Vero cells.
Highlights
In light of the rapid development of coronavirus disease 2019 (COVID-19) vaccines that involves the use of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral stocks for vaccine development, animal studies and human clinical trials, the World Health Organization (WHO) initiated an investigation of the serial propagation of the virus in Vero cells to explore the potential impact of cell substrates on the genetic stability of SARS-CoV-2 virus
Our observations of working stocks of SARS-CoV-2 suggest that sequential propagation in Vero cells leads to critical changes in the region of the furin cleavage site (FCS), which significantly reduce the value of the working stock for critical research studies, vaccine development, production, evaluation and use
Propagating SARS-CoV-2 in Vero E6 cells leads to rapid increases in genetic variants, those located in the sequence coding for the FCS of the spike protein
Summary
In light of the rapid development of coronavirus disease 2019 (COVID-19) vaccines that involves the use of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral stocks for vaccine development, animal studies and human clinical trials, the World Health Organization (WHO) initiated an investigation of the serial propagation of the virus in Vero cells to explore the potential impact of cell substrates on the genetic stability of SARS-CoV-2 virus. An array of SARS-CoV-2 virus variants have been isolated, propagated and used in in vitro assays, in vivo animal studies and human clinical trials. Our observations of working stocks of SARS-CoV-2 suggest that sequential propagation in Vero cells leads to critical changes in the region of the furin cleavage site (FCS), which significantly reduce the value of the working stock for critical research studies, vaccine development, production, evaluation and use
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