How the ‘Eek’ variant could offer long-term clues on adapting COVID-19 vaccines

Variants are a driving force behind new waves of the COVID-19 pandemic and experts worry vaccines aren’t yet equipped to keep up. The so-called “Eek variant” is the latest to make headlines.

It’s not a new variant in itself, it’s a mutation that occurs in different variants. But the mutation’s growing presence, coupled with its behaviour against vaccines, has piqued concern from scientists worldwide.

“It’s a little bit of a worrisome mutation,” said Gerald Evans, chair of the infectious diseases division at Queen’s University in Kingston, Ont.

“Vaccines are going to be effective still and certainly protect you from bad disease, but they will be less effective until we modify them against variants like this, especially if they become dominant.”

For starters, it’s not its own variant, said Colin Furness, an infection control epidemiologist at the University of Toronto.

“It’s not radically different, it’s an adaptation,” he said.

The E484K mutation, nicknamed ‘Eek’ by some, can evade antibody response, making it possible for people to be reinfected or impact how well vaccines work, according to emerging studies.

The mutation targets the spike protein, which allows the virus to infiltrate and hijack our body’s cells. Furness said it’s been dubbed an “escape mutation” because it helps the virus slip past the body’s immune defences.

It’s already been found in the B.1.351 variant first found in South Africa and in some samples of the B.1.1.7 variant identified in the United Kingdom, which is known to spread more easily. The P.1 variant discovered in Brazil, which is also believed to be more contagious, also contains this mutation, said Furness.

The combination of a more transmissible variant that is also better at evading immunity is what has raised alarm, said Furness.

“Something so adaptive like this … We might expect it to dominate more quickly,” he said.

What’s happening is called “convergent evolution,” said Evans.

In other words, the virus is replicating all around the world but particular changes are being favoured, giving it a better chance at surviving or dominating.

“The changes benefit the virus,” Gerald said.

Think of it as the evolution of wild animals, he said. For example, giraffes.

“There’s not just one kind of giraffe, there are northern giraffes in Africa and there are southern giraffes. They both, through evolution, got longer necks. It turned out the long neck was really good for eating. So northern giraffes develop this longer neck, and then southern giraffes develop it,” he said.

“That’s convergent evolution. Both different variants of giraffes got this same mutation, which was a benefit to them, so they survived, whereas the short-necked ones didn’t. Now all the giraffes in the world have long necks.”

The same is happening for COVID-19, he said. However, a silver lining may be that the variants are mutating in a similar way, according to some experts.

Although it will continue to mutate, some scientists suspect this coronavirus may have a fixed number of moves in its arsenal. They say it’s possible the virus only has so many cards to play in adapting its spike protein, where antibody resistance tends to develop.

The idea that the virus could have a limited number of mutations gained traction in February after a pre-print study showed the spontaneous appearance of seven variants in the United States, all in the same region of the spike protein.

The “big four” mutations — N501Y, E484K, L452R and K417N — all seem to be more common and have given the virus an advantage, said Evans, but he’s not convinced it’s “run out of moves.”

“Some virologists believe this is only the beginning and we’ll see more. Others believe if we were going to see more, we probably would’ve already, and what we’re seeing now is four key ones predominating,” he said.

“We’re still in the early part of watching this virus evolve. It’s why getting vaccines out now is so important.”

Scientists have already been checking what these new mutations could mean for existing vaccines. Most were designed around earlier versions of the virus that ignited the pandemic last year.

Early results from Moderna and Johnson & Johnson suggest their vaccines are still effective against variants with this mutation, although the immune response may not be as strong or prolonged. Both vaccines have been approved in Canada.

Scientists also tested Pfizer-BioNTech’s vaccine against E484K and N501Y in the lab and found that the vaccinations appeared to work, but were also slightly less effective.

The fact many of these variants of concern (VOCs) permeating in Canada and the world have similar mutations may enable drugmakers to stay on top of the virus, Furness said.

He believes the E484K mutation only increases the likelihood we will need COVID-19 booster shots down the road.

“That’s not a disaster. With the technology behind mRNA vaccines, it’s easy enough to do,” he said.

But before that happens, we need to get more people vaccinated — and faster, said Evans.

“If we can reduce the number of people infected, the overall number of cases, that puts the virus at a disadvantage,” Evans said.

“It can only mutate when it replicates. If it’s not replicating, it’s just sitting around. It can’t create a new variant.”

Since vaccinations are only now ramping up in Canada, experts say the immediate problem may lie in screening for variants.

“We’re dealing with a lack of data,” said Furness.

The true extent of cases involving this mutation — and many others permeating in Canada — is hard to classify, as only a small fraction of positive COVID-19 cases undergo the genomic analysis necessary to find them.

Canada has scaled up its identification of variants in recent months but as of now, surveillance is laser-focused on the three main VOCs — B.1.1.7, B.1.351 and P.1 — all of which have been detected in Canada.

Ontario is mainly screening for the N501Y mutation, said Evans. If it’s positive, then the sample is screened for the E484K mutation. If that’s positive, it then goes for a comprehensive genome sequencing, which takes about a week or two to complete.

“The problem is, if you’re a variant that contains that ‘Eek’ gene but you don’t have N501Y, you’ll get through the screening process and determined not to be a variant,” he said.

“But you are a variant. It’s just that we’re screening right now for the N501Y mutation first, and secondly for the other.”

Comparisons by province are tricky because every jurisdiction measures and reports its data a little differently. In B.C., where cases of the P.1 variant are soaring, “close to 100 per cent” of positive samples are now screened for variants, the provincial health officer said recently. In Alberta, it stands at around 80 to 85 per cent, Alberta Health Services told Global News.

“Our process is going to have to change,” said Evans. “That’s the sneaky part. We’re going to have to screen for those commoner mutations.”

— with files from Reuters