More than a year into the COVID-19 pandemic, public health authorities are contending with an emerging threat: new variants of the SARS-CoV-2 virus. Researchers around the world have recently identified three notable variants: B.1.1.7, first found in the United Kingdom in December; 501Y.V2, found in South Africa in December; and P1, identified in Brazil on January 13.
There’s no evidence that any of these variants are deadlier than versions of the virus that came before. However, some may be more transmissible due to mutations that alter the coronavirus’s spike protein—the part of the virus that latches on to human cells, and the part that vaccines target. If left unchecked, these variants could spread faster and cause even more death and misery, on top of the more than two million confirmed COVID-19 deaths worldwide through January 15, according to Johns Hopkins University.
However, as vaccine distribution ramps up around the world, researchers are seeing early signs that existing vaccines should work with the body’s multifaceted immune system to offer some level of protection from mutated versions of the virus.
“The variants do have changes in the [virus’s] spike protein, but not enough to make the vaccine not protective,” said Arnold Monto, the acting chair of the U.S. Food and Drug Administration’s Vaccine and Related Biological Products Advisory Committee, in a January 11 interview with the medical journal JAMA. “It looks like [existing vaccines] should work, and we’ll know more definitively in the next couple of weeks.”
To slow the evolution of the virus into new variants, experts say it's critical to do the same things we know prevent the virus's spread—wear masks, wash hands, keep socially distanced, and get vaccinated as soon as possible.
“We have not seen any evidence yet that the new variants are not going to be covered by the vaccine, and, in fact, the way you stop new variants is to contain the virus,” says Philip Dormitzer, chief scientific officer of viral vaccines at Pfizer’s vaccine research division. “The less replication of the virus there is in the world, the fewer variants that are going to get generated.”
If a vaccine-resistant variant of SARS-CoV-2 were to emerge, current vaccines could be tweaked to address any new mutations, Dormitzer adds.
A diverse immune response to COVID-19
Our bodies generate a broad spectrum of antibodies in response to a given vaccine or natural infection. In the case of COVID-19, these antibodies target multiple parts of SARS-CoV-2’s spike protein, not just a single region that could change in a mutated variant of the virus. In principle, this diversity of antibodies makes it harder for a viral mutation to render a vaccine ineffective.
“If there is a mutation that destroys one of the antibody binding regions, in that scenario it will decrease that specific antibody’s binding activity, but there are many, many other antibodies that are not binding to that spot,” says Pei-Yong Shi, a virologist and microbiologist at University of Texas Medical Branch in Galveston.
In addition to antibodies, vaccines also activate T cells—immune cells that play an important role in the body’s early response to SARS-CoV-2, Dormitzer says. Data from vaccine trials suggest that these immune cells might begin to protect the body before large amounts of antibodies are produced.
In Pfizer’s phase three trials, for example, patients who received the first of two doses of the vaccine started to show signs of protection after 10 to 14 days, even though the vaccine’s phase one trials show that many patients don’t necessarily have high levels of antibodies in their blood at that time.
“Either it only takes a tiny amount of neutralizing antibodies to protect against this virus, or something else is protecting that’s not [a] neutralizing antibody,” says Dormitzer, referring to the possible role of T cells in stopping the virus.
In light of our complex immune response to SARS-CoV-2, Dormitzer says that even if vaccine-spurred antibodies don’t bind as well to current or future variants, it’s possible that those vaccines may still confer protection.
This kind of partial protection is already observed in some years’ seasonal flu vaccines, says Helen Chu, an immunologist at the University of Washington in Seattle. “Even if you’re infected with a strain that’s not an exact match to what is in the vaccine, you’re still protected to a degree,” she says. “And these [COVID-19] vaccines are much, much better than the flu vaccines; 95-percent efficacy is much better than the 50 to 60 percent we see with flu.”
Chu, who studies patients’ immune responses to respiratory viruses, has been monitoring COVID-19 since the beginning. Last February, she helped draw the blood of the first confirmed COVID-19 patient in the U.S. Nothing about the arrival of variants surprises her—or reduces her confidence in the broad efficacy of current vaccines.
“I’ve got my vaccine, and I know basically every single scientist and physician I work with is getting the vaccine,” she says. “I would definitely not pause based on the fact that there are new variants emerging.”
Keeping tabs on mutations
For months, researchers have been screening mutated versions of SARS-CoV-2 in the lab with the goal of seeing which mutations pose the greatest risk of increasing the virus’s transmissibility or ability to evade the immune system.
Studies are focusing on the key mutations within the three major emerging variants. Each contains its own array of mutations, but some mutations independently popped up in all three variants—which implies that those particular mutations help the virus spread.
One of the mutations is N501Y, which changes an amino acid within the SARS-CoV-2 spike protein’s receptor binding domain, which is the portion of the protein that directly latches on to the exterior of some human cells. Past research had shown that this mutation could let the virus bind more effectively to ACE2 receptors on human cells, making it more transmissible in humans and other animals. In September, a study published in Science found that the mutation made SARS-CoV-2 more infectious in lab mice.
But this mutation, by itself, doesn’t seem to make the virus resistant to current vaccines. Shi’s lab, in partnership with Pfizer researchers including Dormitzer, used a genetic technique to make two lab versions of SARS-CoV-2 that were identical except for the presence or absence of the N501Y mutation.
In a preliminary study published January 7 on the server bioRxiv, Shi and Dormitzer’s team looked at how antibodies from 20 Pfizer-BioNTech vaccine trial participants responded to the two types of virus. Antibodies attached just as well to the N501Y variant of the virus as the one lacking the mutation. “We’re very happy to see that the results are no compromise of the vaccine,” Shi says.
Even so, Shi readily acknowledges one key limitation to the study: New variants don’t just have single mutations. For instance, the B.1.1.7 variant has eight different mutations that affect its spike protein. In the next two to three weeks, Shi says, his lab will screen different combinations of mutations to further test the Pfizer-BioNTech vaccine.
The 501Y.V2 variant has another mutation of concern: E484K, which also affects the spike protein’s receptor binding domain. In a January 4 preprint published on bioRxiv, researchers at Seattle’s Fred Hutchinson Cancer Research Center found that this mutation plays an outsize role in how well antibodies bind to the virus’s spike protein.
When lab-model viruses with E484K and similar mutations were screened against antibodies from recovered COVID-19 patients, some patients’ antibodies were noticeably less effective at binding to viruses with the mutation. But crucially, the currently authorized vaccines create strong immune responses, and there’s no evidence at present that variants with the E484K mutation will completely resist vaccine-induced immunity.
In a series of posts on Twitter, Jesse Bloom, the preprint’s senior author, made clear that reduced protection is worlds apart from zero protection. “Should we worry about E484K and other mutations? Yes! That's why so many of us are working hard to study them. But we need to keep perspective,” he wrote. “Reduced neutralization does not mean no immunity, and it will take careful study to determine implications for protection in humans.”
What if vaccines need to be modified?
Vaccine manufacturers are laying the groundwork to respond quickly if a future variant of SARS-CoV-2 is unresponsive to existing vaccines. Dormitzer, the Pfizer researcher, says that any changes to the vaccines would have to follow solid clinical observations that a new variant is spreading among people already immunized against COVID-19.
One of the benefits of the Pfizer-BioNTech and Moderna vaccines is that they can be updated quickly. But Dormitzer cautions that laboratory research and manufacturing are just two steps in a vaccine’s long, involved journey to someone’s arm. If a vaccine gets updated, government regulators would need to check whether it’s still safe and effective. Researchers say that policies governing the seasonal flu vaccine’s regular updates could provide a good framework.
“Everyone wants to take flu as the model, and I absolutely agree, flu is our model,” Dormitzer says. But “we need to figure out how we adapt the regulatory pathways—the rules of thumb—that are used for flu for this new virus.”
Crucially, researchers need to know when new variants emerge. All three experts National Geographic interviewed urged governments around the world to vastly increase their genomic sequencing of SARS-CoV-2 and to share the resulting data.
“We really need to very closely monitor the sequences of the viruses in patients,” Shi says. “These are the eyes and ears of our public health.”