Antibodies to the new coronavirus may not work as well against a new variant of the virus identified in South Africa, the first data suggest.
Scientists recently raised questions that the variant, known as 501.V2, may be resistant to COVID-19 vaccines, Live Science previously reported. The experts noted that the variant has accumulated a significant number of mutations in its peak protein, a pointed structure that sticks out from the surface of the virus and attaches itself to human cells to trigger infection.
Authorized vaccines target this peak protein, so if it undergoes a substantial mutation, vaccines may not be as protective. Likewise, antibody drugs and the antibodies that people naturally produce when they get COVID-19 could also be less protective against such a mutant.
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Now, a new study published on January 4 in the prepress 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 The study, which has not been peer-reviewed, found that specific mutations in the spike protein make the variant less vulnerable to some people’s antibodies – but, critically, these mutations do not make the new variant invincible, only less vulnerable to attack. In addition, while some people’s antibodies do not bind well to the variant, others’ antibodies still bind well to the mutant.
“There is wide variation from person to person in how the mutations affect the binding and neutralization of the serum antibody”, which means how well the antibodies stop the virus infect cells, the authors wrote. That said, mutations at one location in the peak protein – called E484 – stood out as a potential problem. For some people, a mutation in E484 meant that the antibodies’ ability to block the virus from entering cells fell more than 10 times.
Unfortunately, 501.V2 has a mutation at site E484, “like some others isolated from elsewhere”, the authors noted in a tweet. This means that the variant may be less vulnerable to antibodies to some people and to antibiotic drugs, but further studies are needed to see whether antibodies generated by the vaccine will be affected in the same way, the authors added.
The team reached these conclusions by zooming in on the “receptor-binding domain” (RBD) of the peak protein, the part of the peak that binds directly to the cell surface. Antibodies come in different flavors, and those targeting RBD are the most critical for neutralizing the coronavirus, according to a study published on Nov. 12 in the journal Cell. Because of this, mutations in the RBD may help new variants to escape the immune system, the authors noted.
The team mapped how different mutations in the RBD would affect its structure and, therefore, 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 “neutralization assays”, the team exposed its mutant yeast to blood serum, the liquid portion of the blood that contains antibodies; these samples were taken from individuals who recovered from COVID-19 and developed antibodies against the virus.
The team also carried out tests with synthetic viruses, called pseudoviruses, which were made to resemble SARS-CoV-2 and were also equipped with mutant RBD, as well as yeast. These pseudoviruses were incubated with human cells and the antibodies sampled, in order to check if the antibodies prevented the infection of the cells.
On average, mutations at the E484 site showed the greatest effect on antibody binding and virus neutralization. That said, at the individual level, “some samples were not affected by the E484 mutations”, and other mutations stood out as a bigger problem, the team noted in their study. For example, some of the samples from recovered patients did not bind so well to RBD with mutations in the so-called “loop 443-450”, a structure that the Regeneron antibody cocktail, called REGEN-COV2, also targets.
As we learn more about the effects of different mutations on immunity against SARS-CoV-2, it will be important to conduct similar studies with antibodies generated by vaccines as well, the authors noted. Fortunately, even the E484 mutations only eroded the neutralizing activity of some of the blood samples tested and didn’t completely eliminate the power of the antibodies in any, the authors tweeted. This increases the likelihood that available vaccines will remain useful “for a long time,” they wrote.
As we continue to monitor the 501.V2 variant, the priority now should be to vaccinate as many people as possible, said Dr. Scott Gottlieb, former commissioner of the Food and Drug Administration, on January 5, CNBC reported.
“The new variant mutated a part of the spike protein to which our antibodies attach, to try to clear the virus itself, so that is worrying,” said Gottlieb. “Now, the vaccine may become a barrier against these variants, which are really taking hold here in the United States, but we need to speed up the pace of vaccination,” he said.
Originally published on Live Science.