Most vaccines under development worldwide have been modelled on the original ‘D-strain’ of the virus, which were more common amongst sequences published early in the pandemic. Since then, the virus has evolved to the globally dominant ‘G-strain’, which now accounts for about 85 per cent of published SARS-CoV-2 genomes. There had been fears the G-strain, or ‘D614G’ mutation within the main protein on the surface of the virus, would negatively impact on vaccines under development, however researchers found no evidence the change would adversely impact the efficacy of vaccine candidates.
Published today in npj Vaccines, the study tested blood samples from ferrets vaccinated with Inovio Pharmaceuticals’ INO-4800 candidate against virus strains that either possessed or lacked this ‘D614G’ mutation.
The study was undertaken in parallel to the pre-clinical trial of INO-4800 at the Australian Centre for Disease Preparedness, CSIRO’s high-containment biosecurity facility in Geelong. CSIRO Chief Executive Dr Larry Marshall said the research was critically important in the race to develop a vaccine. “This brings the world one step closer to a safe and effective vaccine to protect people and save lives,” Dr Marshall said. "Research like this, at speed, is only possible through deep collaboration with partners both in Australia and around the world. “We are tackling these challenges head-on, together, and delivering real world solutions from world-leading Australian science.”
Dr S.S. Vasan, CSIRO’s Dangerous Pathogens Team Leader and the senior author of the paper, said this was good news for the hundreds of vaccines in development around the world, with the majority targeting the spike protein. “Most COVID-19 vaccine candidates target the virus’ spike protein as this binds to the ACE2 receptors in our lungs and airways, which are the entry point to infect cells,” Dr Vasan said.
“Despite this ‘D614G’ mutation to the spike protein, we confirmed through experiments and modelling that vaccine candidates are still effective. “We’ve also found the G-strain is unlikely to require frequent ‘vaccine matching’ where new vaccines need to be developed seasonally to combat the virus strains in circulation, as is the case with influenza.”
Dr Alex McAuley, CSIRO research scientist and first author of the paper, said ferrets vaccinated with INO-4800 demonstrated a strong immune response. “We found that ferrets vaccinated with Inovio Pharmaceuticals’ candidate developed a good B-cell response in terms of neutralising antibodies against SARS-CoV-2 strains, which is important for the short-term efficacy of a vaccine,” Dr McAuley said. “We are also studying the T-cell response which is important for long-term efficacy.”
The Victorian Infectious Diseases Reference Laboratory provided a G-strain isolate from a patient sample to enable this study. The results of the study were further interpreted with biomolecular modelling conducted by CSIRO's digital specialist arm, Data61.
The modelling enabled the interactions between the vaccine and virus to be simulated and visualised, according to Dr Michael Kuiper, co-author and Team Leader of the Molecular & Materials Modelling Group at CSIRO’s Data61.
“If we understand the process of a viral infection, we paint a picture of its vulnerabilities. Bio-molecular modelling helps us to do this,” Dr Kuiper said.
“By visualising molecular structure, we were able to support the study’s inference that the immune response generated by the vaccine candidate is equally effective against both D- and G- strains of SARS-CoV-2.”
CSIRO recently concluded pre-clinical studies for two vaccine candidates (from Inovio Pharmaceuticals and the University of Oxford) at the ACDP, with peer-reviewed reports to be published in the coming months.