SARS-Cov-2 mutations should not affect vaccine viability
The search for a COVID-19 vaccine experienced something of a setback this week, as Johnson & Johnson (J&J) announced that it has temporarily paused all its COVID-19 vaccine trials due to an unexplained illness in a participant in the Phase 3 ENSEMBLE trial.
With the participant’s illness currently being evaluated, both the company and expert commentators have noted that serious adverse events (SAE) are not uncommon in clinical trials, and may well be unrelated to the vaccine itself. That was after all the conclusion of investigations into AstraZeneca’s vaccine candidate, trials of which were briefly suspended in September due to a participant experiencing unexplained neurological symptoms. In the case of J&J, all medical information will be carefully reviewed before a decision is made on whether or not to restart the studies.
But even if the trials do recommence, will they be successful? After all, most COVID-19 vaccines under development worldwide have been modelled on the original ‘D-strain’ of the virus — which was more common amongst sequences published early in the pandemic — but since then the virus has evolved to the globally dominant ‘G-strain’, which now accounts for about 85% of published SARS-CoV-2 genomes. There have therefore 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.
Seeking to resolve this mystery, CSIRO researchers tested blood samples from ferrets vaccinated with Inovio Pharmaceuticals’ INO-4800 candidate against virus strains that either possessed or lacked this D614G mutation. The results of their study, published in the journal npj Vaccines, found no evidence that the change in the virus would adversely impact the efficacy of vaccine candidates.
“Most COVID-19 vaccine candidates target the virus’s spike protein as this binds to the ACE2 receptors in our lungs and airways, which are the entry point to infect cells,” said Dr SS Vasan, CSIRO’s Dangerous Pathogens Team Leader and the senior author of the paper.
“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.”
CSIRO research scientist Dr Alex McAuley, who was first author on the paper, said ferrets vaccinated with INO-4800 “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”. The scientists are also studying the T-cell response, which is important for long-term efficacy, he added.
Meanwhile, the Medical Research Future Fund (MRFF) has granted almost $1 million to a two-year project to determine how long immunity lasts in people who’ve recovered from COVID-19. The project is being run by The University of Queensland (UQ), QIMR Berghofer Medical Research Institute, Monash University, Mater Research and Queensland Health, with UQ’s Dr Kirsty Short saying it serves as an opportunity to understand how long people have immunity to the virus, what kind of immunity they have and whether it’s different for different patients.
“This is important to know because in the advent that it takes a while to get a vaccine, we need to know who is at risk of reinfection, and when there is a vaccine we need to know who is likely to need boosters,” Dr Short said.
Associate Professor Stephanie Gras, from Monash University, said the funding will allow the researchers to provide a deep understanding of the different components of the immune response to infection. “We will focus our effort in understanding what parts of the virus are the most important to target for a protective and long-lived immune response that will be critical in a vaccine,” she said.
QIMR Berghofer’s Associate Professor Corey Smith, lead investigator on the project, said the researchers will be examining immune cells from recovered patients. “Our next step will be to correlate these responses with antibody responses and start to investigate the impact age and co-morbidities have on the quality of the response and how well they are maintained over time,” he said.
“We hope this insight will be important for our understanding of what goes wrong in patients who develop severe complications and to determine which groups of people could remain at risk of infection despite previous exposure.”
If you have recovered from COVID-19 and you are interested in participating in the project, email Covid.DiabetesStudy@mater.org.au.
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