Why scientists are more worried about the Covid-19 variant discovered in South Africa

Scientists are increasingly concerned about a rapidly spreading variant of the virus that causes Covid-19 that was first detected in South Africa. The variant may be more transmissible and could weaken protection from vaccines and prior infections.

There’s evidence from several small, and not-yet-peer-reviewed, studies that mutations in the South Africa variant — known as 501Y.V2 or B.1.351 and already present in at least 23 countries — may lead to reinfections in people who’ve been sick and still should have some immunity.

This 501Y.V2 variant is one of several seemingly more contagious variants of the new coronavirus currently in circulation. For instance, the B.1.1.7 variant that was first identified in the United Kingdom has already spread to several countries, and public health officials expect it will soon become dominant in the US.

But the variant first identified in South Africa is perhaps more alarming because of the prospect that the mutations it contains could limit the effectiveness of existing vaccines, one of the best tools we have for controlling the pandemic.

In their latest report, Moderna — the maker of one of two vaccines on the US market — found the British variant didn’t affect the levels of virus antibodies in the blood of people who had been vaccinated relative to prior variants, but the same wasn’t true for the South Africa strain. “These lower [antibody levels/titers] may suggest a potential risk of earlier waning of immunity to the new B.1.351 strains,” according to a January 25 press release.

The results of this and other recent studies are “a serious indication we have to look hard at how well vaccines might work,” Penny Moore, a virologist at the National Institute for Communicable Diseases in South Africa, told Vox. Taken together, they highlight the dangers of letting Covid-19 spread unchecked, and portend the challenges that lie ahead as the virus continues to evolve.

What the coronavirus variant discovered in South Africa might mean for Covid-19 vaccines

For the Moderna study, which is not yet peer-reviewed, researchers took the blood of eight people who had been vaccinated, as well as two monkeys, and tested it to see how the antibodies responded to the new variants compared with older versions of the virus. The UK variant did not seem to affect an individual’s antibody levels, but the South Africa variant did, reducing them by sixfold relative to older variants.

The company said that even the reduced antibody titers are high enough to still offer protection against the virus, meaning the vaccine will likely still prevent illness stemming from the 501Y.V2 variant. However, it points toward a path of mutations where the level of protection could erode faster than it would against older versions of the virus, increasing the risk of reinfection.

Moderna is now investigating how to reformulate its vaccine to better target the 501Y.V2 variant, while also studying whether an additional booster shot of its current vaccine could increase the levels of antibodies that can neutralize the variant.

The Moderna news comes after studies from other labs have arrived at similar conclusions. For a preprint paper (i.e., non-peer-reviewed) led by Rockefeller University scientists, researchers tested blood samples from 14 people who had received the Moderna vaccine and six who were immunized with the Pfizer/BioNTech vaccine. One particular mutation, named E484K, along with two others found in the South Africa variant, were associated with a “small but significant” drop in antibody activity, the researchers found.

Moore, of the National Institute for Communicable Diseases in South Africa, is the lead author of a new study on 501Y.V2, out as a preprint on BioRxiv. She and her team in South Africa took blood plasma samples from 44 people who had been infected with the coronavirus during the country’s first wave of infections last summer, and checked how their existing antibodies responded to 501Y.V2 as well as older variants.

The researchers sorted the plasma samples into categories — high and low antibody concentrations. In 21 cases — nearly half — the existing antibodies were powerless against the new variant when exposed in test tubes. This was especially true for plasma from people who had a mild previous infection, and lower levels of antibodies, to begin with.

These findings suggest immunity from previous versions of the virus might not help individuals fend off the new variant if they’re exposed, particularly if their prior case was mild or symptom-free.

For Fred Hutchinson Cancer Research Center scientist Trevor Bedford, who was not involved in the research, the study also came as a possible warning sign about the vaccines. As early as autumn this year, manufacturers may need to begin reformulating their shots to respond to the changes in the virus’s genetic code, he wrote on Twitter:

The specific mutation scientists are most worried about

The 501Y.V2 variant carries one mutation of particular concern, known as E484K. This change appears in the part of the virus, the spike protein, that fits into the receptor in human cells. The spike protein is also the major target for the currently available mRNA vaccines, from Pfizer/BioNTech and Moderna.

“This mutation sits right in the middle of a hotspot in the spike,” Moore said. And it’s become notorious among virologists for its ability to elude coronavirus antibodies.

Scientists have demonstrated how this might happen in other cell culture experiments. A new study, also in preprint form from South African researchers, took a similar approach to Moore’s — testing how antibodies from six convalescent plasma donors react to 501Y.V2. But this time they used live virus, considered “the gold standard for these experiments,” said study co-author Richard Lessells, a University of KwaZulu-Natal infectious disease specialist. And their findings pointed in the same direction: 501Y.V2 can — at least in the lab — escape the antibody response elicited from a prior infection, and the E484K mutation “has the clearest association with immune escape.”

In another recently published BioRxiv preprint, researchers in Washington state tracked how mutations altered the effectiveness of the antibody response in convalescent plasma of 11 people — and also found E484K had particularly potent antibody evasion capabilities.

Other variants of concern also carry the E484K mutation, including one first identified in Manaus, Brazil, known as P.1. And one case study suggests reinfection in some people might be possible when they’re exposed to the new variant.

In a preprint, researchers in Brazil documented the case of a 45-year-old Covid-19 patient with no comorbidities, who, months after her first bout with the illness, was reinfected with the new variant. The patient experienced more severe illness the second time around. While it’s limited evidence, it “might have major implications for public health policies, surveillance and immunization strategies,” the authors wrote.

The study’s broader context is also concerning: After up to three-quarters of the population in Manaus, Brazil, was estimated to be infected with the virus during a spring surge, cases are piling up again and hospitals are filling up. Researchers suspect reinfections with the new variant could be a driver.

“The news is not all grim”

But “the news is not all grim,” said University of Utah evolutionary virologist Stephen Goldstein. The Rockefeller University preprint found antibodies from the vaccine may be more potent than antibodies from a previous infection. And the antibodies induced by the vaccines “are so high to start with that the serum was still extremely potent against the mutant.”

To fully understand the threat the mutations pose to vaccines, we’ll need clinical trials involving vaccinated people, Moore said. “These studies flag a problem,” she added, “but how that translates to real life, we can’t tell.”

There’s also huge variation in immune responses among people, Goldstein said. In the Washington paper, the researchers found “extensive person-to-person variation” in how the mutations affected an individual’s antibody response.

“The bottom line there is some reason for concern about reduced efficacy, but efficacy will not fall off a cliff,” Goldstein said. “The vaccines are incredibly potent. … If [they go] from 95% [efficacy] to 85% or even a little lower, we are still in great shape.” That’s why researchers and public health officials are heavily advocating for everyone to be vaccinated as quickly as possible.

Even so, Moore cautioned: “From an immune escape point of view, the variants first detected in Brazil and South Africa are more of a concern, but this is just the beginning. It’s our first indication that this virus can and does change.”

It’s possible that as we learn more, even the E484K mutation won’t turn out to undermine the vaccines. But there may be other changes to the virus lurking out there or evolving that will escape even vaccine-induced antibodies. “So many people now are infected that this is an arms race — the virus is now given every opportunity to mutate,” Moore said, “so it can take those steps on the pathway to immune escape more easily.”

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