Experimental and in silico evidence suggests vaccines are unlikely to be affected by D614G mutation in SARS-CoV-2 spike protein

Alexander J McAuley; Michael J Kuiper; Peter A Durr; Matthew P Bruce; Jennifer Barr; Shawn Todd; Gough G Au; Kim Blasdell; Mary Tachedjian; Sue Lowther; Glenn A Marsh; Sarah Edwards; Timothy Poole; Rachel Layton; Sarah-Jane Riddell; Trevor W Drew; Julian D Druce; Trevor R F Smith; Kate E Broderick; S S Vasan

doi:10.1038/s41541-020-00246-8

Experimental and in silico evidence suggests vaccines are unlikely to be affected by D614G mutation in SARS-CoV-2 spike protein

NPJ Vaccines. 2020 Oct 8:5:96. doi: 10.1038/s41541-020-00246-8. eCollection 2020.

Authors

Alexander J McAuley¹, Michael J Kuiper², Peter A Durr¹, Matthew P Bruce¹, Jennifer Barr¹, Shawn Todd¹, Gough G Au¹, Kim Blasdell¹, Mary Tachedjian¹, Sue Lowther¹, Glenn A Marsh¹, Sarah Edwards¹, Timothy Poole¹, Rachel Layton¹, Sarah-Jane Riddell¹, Trevor W Drew¹, Julian D Druce³, Trevor R F Smith⁴, Kate E Broderick⁴, S S Vasan^{1

5}

Affiliations

¹ Commonwealth Scientific and Industrial Research Organisation, Australian Centre for Disease Preparedness, Geelong, VIC 3219 Australia.
² Commonwealth Scientific and Industrial Research Organisation, Data61, Docklands, VIC 3008 Australia.
³ Victorian Infectious Diseases Reference Laboratory, The Royal Melbourne Hospital at The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000 Australia.
⁴ Inovio Pharmaceuticals, 10480 Wateridge Circle, San Diego, CA 92121 USA.
⁵ Department of Health Sciences, University of York, York, YO10 5DD UK.

Abstract

The 'D614G' mutation (Aspartate-to-Glycine change at position 614) of the SARS-CoV-2 spike protein has been speculated to adversely affect the efficacy of most vaccines and countermeasures that target this glycoprotein, necessitating frequent vaccine matching. Virus neutralisation assays were performed using sera from ferrets which received two doses of the INO-4800 COVID-19 vaccine, and Australian virus isolates (VIC01, SA01 and VIC31) which either possess or lack this mutation but are otherwise comparable. Through this approach, supported by biomolecular modelling of this mutation and the commonly-associated P314L mutation in the RNA-dependent RNA polymerase, we have shown that there is no experimental evidence to support this speculation. We additionally demonstrate that the putative elastase cleavage site introduced by the D614G mutation is unlikely to be accessible to proteases.

Keywords: SARS-CoV-2; Vaccines; Viral evolution.