Most vaccines under development have been modelled on the original D-strain of the virus, which was predominant among the sequences published early in the pandemic.
However, the virus’ main strain globally is now the G-strain (accounting for around 85% of published SARS-CoV-2 genomes): a result of a mutation on the main protein on the surface of the virus.
In a study published this month in npj Vaccines, researchers say there is no evidence this D614F mutation would adversely impact the efficacy of vaccine candidates – important as the majority of candidates target the spike protein.
Biomolecular models
The study from CSIRO, Australia’s national science agency, vaccinated ferrets with Inovio Pharmaceutical’s DNA vaccine candidate INO-4800 against virus strains both with and without the D614G mutation (This was done in parallel to the pre-clinical trial of INO-4800).
It also created biomolecular models to visualise interactions between vaccine and virus.
The vaccinated ferrets were found to have developed a ‘good B-cell response in terms of neutralising antibodies against SARS-CoV-2 strains’, while researchers are also looking at the T-cell response for long-term efficacy.
They also found that, given the positioning of the G614 variant, a ‘lack of adverse effects on neutralisation efficiency of antibodies generated following vaccination with D614-derived vaccines is not unexpected’.
COVID-19 vaccine candidates primarily target the trimeric ‘spike’ (S) glycoprotein, as this factor enables binding to the ‘angiotensin-converting enzyme 2’ (ACE2) host surface receptors and facilitates virus entry into the cells.
In recent months, an Aspartate-to-Glycine amino acid change has arisen at position 614 of the S protein (resulting from a single A-to-G nucleotide change at position 23,403 in the Wuhan-Hu-1 reference genome).
This mutation has led scientists to suggest that the D614G mutation gives the virus a structural advantage; and led to speculation that the efficacy of vaccines and countermeasures which target the S protein could be adversely affected, requiring frequent vaccine matching.
However, the CSIRO study says there is no evidence for this.
Dr S.S. Vasan, CSIRO’s Dangerous Pathogens Team Leader and the senior author of the paper, said the study’s findings are good news for the hundreds of vaccines in development around the world, particularly given that the majority target 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,” said Dr Vasan.
“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.”
The researchers are urging scientists to exercise caution when describing virus mutations in pre-print articles. “Premature inferences on their effects without supporting experimental evidence could result in a media frenzy and potentially undermine public confidence in vaccines,” they note.
