Common mutation may make novel coronavirus more vulnerable to vaccine, says study
A common mutation in the novel coronavirus that has enabled it to spread quickly around the world may also make it more susceptible to a vaccine, according to a study that proves some of the first concrete findings about how SARS-CoV-2, which causes COVID-19, is evolving.
Researchers at the University of North Carolina at Chapel Hill and the University of Wisconsin-Madison in the US noted that the new strain of coronavirus, called D614G, emerged in Europe and has become the most common in the world.
Their study, published in the journal Science, shows the D614G strain replicates faster, and is more transmissible than the virus, originating in China, that spread in the beginning of the pandemic.
While the D614G strain spreads faster, in animal studies it was not associated with more severe disease, and the strain is slightly more sensitive to neutralisation by antibody drugs, the researchers said.
“The D614G virus outcompetes and outgrows the ancestral strain by about 10-fold and replicates extremely efficiently in primary nasal epithelial cells, which are a potentially important site for person-to-person transmission,” said Ralph Baric, a professor at the UNC-Chapel Hill.
Researchers believe the D614G strain of coronavirus dominates because it increases the spike protein’s ability to open cells for the virus to enter.
The D614G mutation causes a flap on the tip of one spike to pop open, allowing the virus to infect cells more efficiently but also creating a pathway to the virus’ vulnerable core, the researchers said.
With one flap open, it’s easier for antibodies — like the ones in the vaccines currently being tested — to infiltrate and disable the virus, they said.
“The original spike protein had a ‘D’ at this position, and it was replaced by a ‘G,'” said Yoshihiro Kawaoka , a virologist at the University of Wisconsin-Madison.
“Several papers had already described that this mutation makes the protein more functional and more efficient at getting into cells,” Kawaoka said.
That earlier work, however, relied on a pseudotyped virus that included the receptor-binding protein but was not authentic, the researchers said.
Using reverse genetics, Baric’s team replicated a matched pair of mutant SARS-CoV-2 viruses that encoded D or G at position 614 and compared basic property analysis using cell lines, primary human respiratory cells, and mouse and hamster cells.
The University of Wisconsin-Madison researchers performed replication and airborne transmission studies with both the original virus and the mutated version.
They found that the mutated virus not only replicates about 10 times faster — it’s also much more infectious.
Hamsters were inoculated with one virus or the other. The next day, eight uninfected hamsters were placed into cages next to infected hamsters.
There was a divider between them so they could not touch, but air could pass between the cages.
Researchers began looking for replication of the virus in the uninfected animals on day two. Both viruses passed between animals via airborne transmission, but the timing was different.
With the mutant virus, the researchers saw transmission to six out of eight hamsters within two days, and to all the hamsters by day four.
With the original virus, they saw no transmission on day two, though all of the exposed animals were infected by day four.
“We saw that the mutant virus transmits better airborne than the original virus, which may explain why this virus dominated in humans,” Kawaoka said.
The researchers also examined the pathology of the two coronavirus strains.
Once hamsters were infected, they presented essentially the same viral load and symptoms.
This suggests that while the mutant virus is much better at infecting hosts, it doesn’t cause significantly worse illness, they said.
However, the researchers caution that the pathology results may not hold true in human studies.
