Coronavirus May Have Mutated to Become More Infectious. What Does That Mean for a Vaccine?
Scientists believe there are two types of the COVID-19-causing coronavirus, with one more infectious than the other. The mutation affects the spike protein on the virus's surface, which it uses to invade our cells, according to the study published in the journal Cell.
The study raises questions about the development of vaccines focusing on the spike protein of SARS-CoV-2, the virus that causes COVID-19. Would, for instance, basing research on what may be a less infectious or dominant form of the virus be a waste of time? However, experts told Newsweek it is unlikely the mutation will affect the process, although it is important to monitor such changes.
The authors originally released their work on the pre-print website bioRxiv in May (meaning it hadn't been peer-reviewed) prompting debate online. Since then, it has been peer-reviewed and the team has conducted more experiments in a bid to bolster their findings.
Writing in the journal Cell, the team detailed their exploration of SARS-CoV-2 mutations. Although they sound alarming, these are a normal and generally inconsequential part of the life-cycle of germs.
The scientists said the variants named D614 and G614 have differences in what is known as an amino acid that makes up the spike protein. Proteins, the building blocks of life, are comprised of amino acids. According to the team, this appears to have made G614 more infectious. However, other experts in the field aren't entirely convinced.
There were many parts to the study. In one, the researchers used an international database of the genetic make-up of different samples of SARS-CoV-2, and looked at 28,576 sequences they downloaded in late May. This enabled them to see where the two variants had spread in different locations.
Over the course of about a month, G614 had become the globally dominant form of SARS-CoV-2, the authors said. Prior to March 1 it was found in 10 percent of the 997 global sequences, but 78 percent of the 12,194 sequences between April to mid-May.
To check whether the variants could affect how sick COVID-19 patients got, the team also examined the genetic sequences SARS-CoV-2 collected from 999 COVID-19 patients in the U.K. Samples from patients infected with the G614 variant had higher levels of the virus's genetic material, called RNA, but this didn't appear to make the patients more ill.
In lab studies, the team took pseudoviruses, essentially replicas of SARS-CoV-2, and watched to see if they could infect human cells. They found the G614 variant was between three to six times more infectious.
They also used antibodies from the blood of six San Diego residents who were likely infected in early to mid-March when both D614 and G614 were circulating. Antibodies were equally effective at neutralizing either variant, but it's not clear which of the virus the individuals were infected with, the team said.
According to the authors, it will be important to determine whether the variants behave differently with antibodies either triggered by vaccinations or natural infection. It may be the case that if G614 is more infectious, it will need higher antibody levels for protection by vaccines or antibody therapeutics.
A database documenting mutations of SARS-CoV-2 sequences that is updated daily could help researchers develop vaccines and design future experiments, the researchers said. "The speed with which G614 variant became the dominant form globally suggests the need for continued vigilance," they wrote.
Co-author Bette Korber, a fellow at Los Alamos National Laboratory (LANL), said in a statement that her team's direct experience in working with HIV, that a single amino acid change can have a "major" impact on the characteristics of a virus.
However, the study was limited for a number of reasons. For instance, the team said, G614 may pop up more frequently because more people with that variant are being tested. In addition, the team use neither a virus from the wild in their lab studies, nor respiratory cells that SARS-CoV-2 often targets.
And while it is possible that G614's "rapid spread and persistence" could be explained by its higher infectivity, it's likely a combination of factors, such as the virus finding itself in well-connected populations, helped its rise, they said.
Academics not involved in the study stressed to Newsweek the team weren't able to prove that G614 is more infectious.
Richard Goldstein, professor of pathogen evolution at University College London, told Newsweek via email that, for a number of reasons, the statistical evidence the team provides for the effect of the mutation on how the virus behaves "is likely highly overstated, and the conclusions of Korber and colleagues remains highly tentative."
He said: "Virus transmission patterns are incredibly complicated, involving an interplay between travel patterns, cultural attributes, the physical environment, family structures, government policies, public health measures, et cetera."
By using simple models to explain such a complex situation "it is easy to identify patterns in the transmission dynamics that seem highly statistically significant, but can easily be explained by the limitations of the simple models," he said.
"This, paradoxically, increasingly becomes a problem as we get more and more data, providing us with an enhanced ability to justify spurious results. For this reason, it is important to be careful about the interpretations of such simple models, and recognize that the measures we used to identify statistical significance may rely on the same assumptions as the overly simplistic models."
More studies need to be done to show that this mutation actually has an effect on the virus, Goldstein said.
Lawrence Young, professor of Medical Oncology, at the U.K.'s University of Warwick, said in a statement: "The data suggesting that the G614 variant is more infectious is intriguing but these studies were performed in a very artificial system and require verification."
Asked whether it is likely the mutation explains why some parts of the world appear to have been hit harder than others by COVID-19, Oscar MacLean, a bioinformatician at the Centre for Virus Research at the University of Glasgow, U.K., told Newsweek via email this is unlikely.
"In European countries where this mutation has been at high frequency for a while, the virus has —for the most part—now been successfully suppressed. Therefore, variation in human behavior rather than variation in the viral genome seems to best explain this regional variation."
He went on: "The virus was capable of exponential growth before and after this mutation (and others) rose to high frequency, it should serve as a reminder to be vigilant with our behavior and avoid letting that exponential growth take off again."
What does this mean for a vaccine?
Addressing concerns the mutation may affect vaccine development, Lawrence said it "only makes a very small change in the spike protein of the virus.
"While the spike protein is the main component of most of the vaccines that are being developed, this small change is unlikely to have any impact on the effectiveness of a vaccine.
"However, if the data indicating that this mutation increases the infectiousness and replication efficiency of the virus is confirmed, it may be that any vaccine would need to induce a higher level of immunity to provide protection."
It is also important to consider other changes in different parts of the virus, he said. "We need to keep an eye on these other changes and how they are spreading in different populations as well as what this means for both vaccine development and antiviral drug therapies."
MacLean similarly said the location of the mutation means it's likely to have little impact on vaccines, but new mutations should always be a consideration for vaccine developers.
"I don't think this mutation is going anywhere, but it's important to remember that viruses mutate quickly and this mutation is not the only one that will accumulate over time," he said.
Ian Jones, professor of virology at the University of Reading, U.K, said there is no suggestion it would change the effectiveness of a vaccine made with sequences that did not contain this mutation. "So, [the mutation is] evolution in action, but not to anything more alarming than what we are currently seeing."
