Can the COVID-19 Vaccine Beat the Proliferation of New Virus Mutations?

By Lawrence Wright, The New Yorker

23 January 21

ll viruses change. SARS-CoV-2 had been remarkably stable as it coursed around the world, being so well adapted to the human host. This stability allowed the development of vaccines that are finely targeted for vulnerable regions of the virus’s spike protein. In February, 2020, a new variant emerging from Italy proved to be more infectious than the original Wuhan variant. Scientists were on guard, expecting an assault of new mutations. “We were getting sequencing up and running” to detect new variants, Gregory Armstrong, the director of the Advanced Molecular Detection program at the Centers for Disease Control and Prevention, told me. “Then for ten months, it was crickets.”

Last September, just as the first vaccine candidates were undergoing their Phase III trials, an aggressive new variant began circulating in southeast England, centered in Kent, along the highway from London to Dover. On Halloween, England announced a monthlong lockdown, which was dramatically successful in curbing the spread of COVID-19 in other parts of the country, but not in the Kent corridor. There were already a number of distinct variants of the novel coronavirus, with a few genetic variations of little consequence. But the U.K. variant, initially labelled a “Variant Under Investigation,” contained twenty-three different mutations, including several on the spike protein; moreover, it was rapidly driving out competitors and becoming the predominant virus in the country, especially among younger people. On December 18th, it was upgraded to a “Variant of Concern.”

What made the U.K. variant so much more successful than the original virus? One possibility is pure chance. It could have been amplified through some superspreader event, like the variant that took root at an employee conference at the Boston biotech firm Biogen, in February, 2020, which eventually accounted for more than three hundred thousand infections. Or perhaps it got seeded in a school or a church, and spread rapidly among a tightly knit population. But, as researchers went back and studied the growth of the U.K. variant’s mutations through serum samples, they realized that neither of these hypotheses could account for the accelerated pace of the spread. “Some mathematicians modelled how the variant has spread, and they found it was between forty and seventy per cent more infectious,” John Brooks, the chief medical officer at the Centers for Disease Control’s COVID-19 Emergency Response, told me. The current hypothesis is that the Kent variant, now called B.1.1.7, has a mutation that switched an amino acid in the spike protein, allowing it to bind more tightly to the body’s ACE2 receptors. “That means it takes less virus to infect you,” Brooks said. “That tighter binding also means that it can replicate more efficiently.” Once infected with the new variant, a person will be shedding more virus than someone infected with another variant. “It’s a wicked cycle,” Brooks observed. B.1.1.7 quickly spread to dozens of countries. The ongoing mystery is why it is not more fatal, given its increased viral load. It may be just a matter of luck.

England entered lockdown once again. By the second week in January, one in thirty people in London was infected. The worrisome mutation in the B.1.1.7 variant affects the area of the virus where the antibodies that neutralize the disease do their work. The new mRNA vaccines present a modified spike protein to the body, alerting the immune system to a foreign invader and commanding the production of antibodies. It appears that B.1.1.7 partially alters the main target on the spike protein. That set off alarms in the public-health community, because such mutations could erode the effectiveness of the vaccines. Viruses are always looking for hidden opportunities that mutations create, much as hackers search out flaws in application codes.

A month after the new variant was uncovered in England, a similar lineage emerged in South Africa, called B.1.351. It quickly became the dominant variant in that country and began its own tour of the world. It has the same mutation as B.1.1.7, which allows it to adhere more tightly to the ACE2 receptors, but it also carries an additional mutation that is far more concerning. The mutation is denominated E484K, meaning that the amino acid, glutamic acid (code letter E), has been replaced by another, lysine (code letter K), in position 484 of the genetic sequence of the spike protein. This tiny alteration may possibly make the vaccine less effective against it. In a lab experiment, the E484K mutation caused greater than tenfold drop of immunity in the antibodies of some COVID-19 survivors. The vaccines that are being deployed now should still be effective, researchers have said, but clearly the virus is evolving new strategies that make it more contagious and less able to be corralled by a vaccine.

Yet another dangerous variant, B.1.1.28, turned up in Brazil. A forty-five-year-old health-care worker in the northeastern part of the country, who had no comorbidities, got COVID-19 in May of 2020. She was sick for a week with diarrhea, muscle aches, exhaustion, and pain while swallowing, but she fully recovered. Then, in October, a hundred and fifty-three days later, she fell ill again with COVID-19, and, this time, the disease was more severe.

“This made the hair on my neck stand up,” Brooks said. Like the South African variant, the Brazilian variant does have the mutation that makes it more infectious, and it also has the E484K mutation, which raises the unsettling possibility that “it could possibly overcome the vaccine, and it may reinfect.” He compares the coronavirus to the flu or the common cold, which are constantly changing, dodging the body’s immune system. Gregory Armstrong told me of an experiment to determine how many mutations it would take to create what is known as an “immune escape” strain. “They grew it up in tissue culture from a generic SARS-CoV-2 in dilute convalescent sera,” he said. “They were eventually able to grow one that had three mutations that conferred almost complete resistance” to the antibodies in the survivors’ blood.

“So how do we fight these mutants?” Brooks asked. “The best way is to suppress replication—and that means stopping infections.” The more replications that occur, the greater the number of mutations. Occasionally, a slight error in replicating the genetic code creates a mutant variant that spreads more successfully and, when that happens, evolution takes over. Stopping transmission blocks the opportunity for viral mutation; it’s the only thing that does. And the only means we have of standing in the way of the virus is vaccination. “It’s a race,” Brooks said. “We’ve got to get people vaccinated before more of these mutations occur.”

The World Health Organization says that herd immunity is reached when sixty to seventy per cent of the population has had the disease or a vaccination, although Anthony Fauci has upped the figure incrementally, now saying that a more reliable figure may be between eighty-five and ninety per cent. The increased transmissibility of the mutant variants makes the higher figures more likely.

The C.D.C. predicts that B.1.1.7 will be the predominant variant in the U.S. by March, and is warning overburdened hospitals to expect another surge, which will outrace the immunization process now underway. If stricter masking and social-distancing measures are not taken, and the vaccine is not given more time to make an impact, the coronavirus will become endemic. In fact, that appears to be happening already, with the proliferation of mutant variants, although stricter measures could mitigate the spread.

On January 19th, two preprint research papers were published. One had good news: the Pfizer vaccine (and because it is highly similar, probably the Moderna one) was just as effective in blocking the B.1.1.7 variant as the virus that originated in Wuhan. The other paper contained findings that Brooks and others have been dreading: the South African variant, B.1.351, has shown that it can escape the antibodies in the blood of previously infected persons. This suggests that the therapies that use what are called monoclonal antibodies—such as what President Trump received—could fail. The authors of the study, led by Kurt Wibmer, at the National Institute for Communicable Diseases, in Johannesburg, underscored the implications for the effectiveness of SARS-CoV-2 vaccines, which are based on immune responses to the spike protein. “These data highlight the prospect of reinfection with antigenically distinct variants and may foreshadow reduced efficacy of current spike-based vaccines.”