Antibodies to the new coronavirus may not work as well against a new variant of the virus identified in South Africa.
Scientists have recently expressed concern that the variant, known as 501.V2, may be resistant to COVID-19 vaccines, Live Science reported earlier. Experts have noted that the variant accumulates a significant number of mutations in its collection ear protein, a pointed structure that adheres to the surface of the virus and binds to human cells to cause infection.
The authorized vaccines are targeted at this vein protein, so if it mutates substantially, the vaccines may not be as protective. Similarly, antibody products and the antibodies that humans naturally produce when they catch COVID-19 may also be less protective against such a mutant.
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Now a new study has been placed in the pre-print database on January 4th bioRxiv suggests that this may be the case with 501.V2. The study, which was not evaluated by the peer, found that specific mutations in the peak 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 attacks. While some people’s antibodies may not bind well to the variant, others’ antibodies still bind well to the mutant.
“There is an extensive person-to-person variation in how mutations affect binding and neutralization of the antibody on serum,” which means how well the antibodies virus of the infection of cells, the authors wrote. That said, mutations at one site on the vein protein – called E484 – have been identified as a possible problem. For some people, a mutation at E484 means that the antibodies’ ability to block the virus in the cells has dropped more than ten times.
Unfortunately, 501.V2 has a mutation at the E484 site, ‘just like other isolates from elsewhere’, the authors in a tweet. This means that the variant may be less vulnerable to antibodies and antibody products for some people, but more studies are needed to know whether vaccine-generated antibodies will also be affected.
The team came to these conclusions by zooming in on the “receptor binding domain” (RBD) of the vein protein, the part of the vein that binds directly to the cell surface. Antibodies come in different flavors, and those targeting the RBD are the most important for neutralizing the coronavirus, according to a study published in the journal on November 12. Cell. As a result, mutations in the RBD may help to evade new variants. 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 have genetically modified yeast cells to grow the mutant RBD on their surfaces. In experiments called ‘neutralizing tests’, the team exposed their mutant yeast to blood serum, the liquid portion of blood that contains antibodies; these samples were taken from individuals who had recovered from COVID-19 and developed antibodies against the virus.
The team also conducted tests with synthetic viruses, called pseudoviruses, which were made to look like SARS-CoV-2 and also just like the yeast were equipped with mutant RBD. These pseudoviruses were incubated with human cells and the sampled antibodies to see if the antibodies prevented the cells from becoming infected.
On average, mutations at the E484 site showed the greatest effect on antibody binding and neutralization of the virus. That said, on an individual level, ‘some samples were essentially unaffected by E484 mutations’, and other mutations posed a bigger problem, the team noted in their paper. For example, some samples from recovering patients did not bind as well to RBD with mutations in the so-called “443-450 loop”, a structure to which the Regeneron antibody cocktail, called REGEN-COV2, is also directed.
As we learn more about the effects of different mutations on SARS-CoV-2 immunity, it is important to conduct similar studies with vaccine-generated antibodies as well. Fortunately, even the E484 mutations only eroded the neutralizing activity of some of the tested blood samples, and they did not completely eradicate the power of the antibodies, tweeted the authors. This increases the likelihood that available vaccines will retain their usefulness ‘for another while’, they write.
While we continue to monitor the 501.V2 variant, the priority should be to vaccinate as many people as possible, said dr. Scott Gottlieb, former commissioner of the Food and Drug Administration, said on January 5th. CNBC reported.
“The new variant has mutated some of the ear protein to which our antibodies bind to clear up the virus itself. So it’s worrying,” Gottlieb said. “Now, the vaccine could be a turning point against these variants that are really gaining a foothold here in the United States, but we need to speed up the rate of vaccination,” he said.
Originally published on Live Science.