Antibodies against the novel coronavirus may not work as well against a new variant of the virus identified in South Africa, early data suggest.
Scientists recently raised concerns that the variant, known as 501.V2, may be resistant to COVID-19 vaccines, Live Science previously reported. Experts noted that the variant has accumulated a significant number of mutations in its spike protein, a pointed structure that sticks off the virus’s surface and binds to human cells to trigger infection.
The authorized vaccines target this spike protein, so if it mutates substantially, the vaccines may not be as protective. Similarly, antibody drugs and the antibodies that people naturally produce when they catch COVID-19 could also be less protective against such a mutant.
Now, a new study posted Jan. 4 to the preprint database bioRxiv suggests that this may be the case with 501.V2. The study, which has not been peer-reviewed, found that specific mutations in the spike protein make the variant less vulnerable to some people’s antibodies — but critically, these mutations don’t make the new variant invincible, only less vulnerable to attack. Additionally, while some people’s antibodies couldn’t bind well to the variant, others’ antibodies still bound well to the mutant.
“There is extensive person-to-person variation in how mutations affect serum antibody binding and neutralization,” meaning how well the antibodies stop the virus from infecting cells, the authors wrote. That said, mutations at one location on the spike protein — called E484 — stood out as a potential issue. For some people, a mutation at E484 meant the antibodies’ ability to block the virus from entering cells fell more than 10-fold.
Unfortunately, 501.V2 has a mutation at the E484 site, “as do some other isolates from elsewhere,” the authors noted in a tweet. That means that the variant may be less vulnerable to some people’s antibodies and to antibody drugs, but more studies are needed to know whether vaccine-generated antibodies will be similarly affected, the authors added.
The team reached these conclusions by zooming in on the “receptor binding domain” (RBD) of the spike protein, the part of the spike that directly binds to the cell surface. Antibodies come in different flavors, and those that target the RBD are the most critical for neutralizing the coronavirus, according to a study published Nov. 12 in the journal Cell. Because of this, mutations in the RBD could help new variants evade the immune system, the authors noted.
The team mapped how different mutations in the RBD would affect its structure and thus the ability of antibodies to bind to it; they then genetically modified yeast cells to grow the mutant RBD on their surfaces. In experiments called “neutralizing assays,” the team exposed their mutant yeast to blood serum, the liquid portion of blood that contains antibodies; these samples were drawn from individuals who had recovered from COVID-19 and developed antibodies against the virus.
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The team also conducted assays with synthetic viruses, called pseudoviruses, which were made to resemble SARS-CoV-2 and were also equipped with mutant RBD, just like the yeast. These pseudoviruses were incubated with human cells and the sampled antibodies, in order to see whether the antibodies stopped the cells from becoming infected.
On average, mutations at the E484 site showed the largest effect on antibody binding and neutralization of the virus. That said, at the individual level, “a few samples were essentially unaffected by E484 mutations,” and other mutations stood out as a bigger problem, the team noted in their paper. For example, some of the samples from recovered patients did not bind as well to RBD with mutations in the so-called “443-450 loop,” a structure that the Regeneron antibody cocktail, called REGEN-COV2, also targets.
As we learn more about the effects of different mutations on SARS-CoV-2 immunity, it will be important to run similar studies with vaccine-generated antibodies, too, the authors noted. Thankfully, even the E484 mutations only eroded the neutralizing activity of some of the blood samples tested, and they didn’t completely wipe out the antibodies’ power in any, the authors tweeted. That raises the likelihood that available vaccines will retain their usefulness “for quite a while,” they wrote.
While we continue to monitor the 501.V2 variant, the priority now should be to vaccinate as many people as possible, Dr. Scott Gottlieb, former commissioner of the Food and Drug Administration, said on Jan. 5, CNBC reported.
“The new variant has mutated a part of the spike protein that our antibodies bind to, to try to clear the virus itself, so this is concerning,” Gottlieb said. “Now, the vaccine can become a backstop against these variants really getting more of a foothold here in the United States, but we need to quicken the pace of vaccination,” he said.