UK genome analysis has important implications for COVID-19 clinical trials


Scientists at the University of Liverpool who have been sequencing genetic material from SARS-CoV-2 — the virus that causes COVID-19 — in collaboration with the University of Bristol and Public Health England have highlighted important implications for scientists around the world conducting vaccine trials aimed at preventing the disease. The findings are published on the preprint site bioRxiv.

Using state-of-the-art scientific techniques, the team isolated parts of SARS-CoV-2 to find out how the virus instructs the cell to make virus proteins, which can either be used to form virus particles or slow our immune response. The team was also able to investigate whether the genome of the virus changes during growth in cells. These cells are used to study the virus and also for vaccine research.

In this paper, the researchers show that when the virus was grown in the laboratory in monkey cells significant changes to the protein found on the surface of the virus occurred. This is called the “spike glycoprotein” which promotes entry into the host cell and is an important target for the human immune system in its fight against the virus.

Importantly, the findings have implications for scientists conducting vaccine research and those searching for synthetic antibodies to treat infection. Because, when grown on a large scale in the laboratory, the virus might alter the spike glycoprotein. Such a change may mean that when this altered virus is used in important animal clinical trials it might make it harder or impossible to understand if a vaccine or synthetic antibody is working or not.

The work builds on many years of research on coronaviruses and sequencing high consequence infections by the team at Liverpool, led by Professor Julian Hiscox, and the Bristol team led by Dr Andrew Davidson and Dr David Matthews from Bristol’s School of Cellular and Molecular Medicine. The teams have been working alongside colleagues from the Public Health England (PHE).

The study was supported by the United States Food and Drug Administration (FDA). Professor Hiscox is also supported by Liverpool’s COVID-19 research consortium.

Pre-print reference:

'Characterisation of the transcriptome and proteome of SARS-CoV-2 using direct RNA sequencing and tandem mass spectrometry reveals evidence for a cell passage induced in-frame deletion in the spike glycoprotein that removes the furin-like cleavage site' by Andrew D. Davidson, Maia Kavanagh Williamson, Sebastian Lewis, Deborah Shoemark, Miles W. Carroll, Kate Heesom, Maria Zambon, Joanna Ellis, Phillip A. Lewis, Julian A. Hiscox, David A. Matthews in bioRxiv