Focusing on antibodies that target conserved sites on virus spike protein may help overcome variants
Scientists have identified antibodies that can target the unchanged parts of the novel coronavirus as it continues to mutate and evolve, an advance that could lead to new therapeutics to neutralise Omicron and other Covid-19 variants.
Identifying such “broadly neutralising” antibodies on the coronavirus spike protein, which the virus uses to enter human cells, can help develop better vaccines and antibodies which will be effective not only against Omicron but also against other variants that may emerge in the future, said David Veesler from the University of Washington School of Medicine in the US.
“This finding tells us that by focusing on antibodies that target these highly conserved sites on the spike protein, there is a way to overcome the virus’ continual evolution,” Dr Veesler said in a statement.
So far, studies have shown that Omicron has 37 mutations in the spike protein, which partly explains why this variant has been able to spread so rapidly, infecting people who have already been vaccinated and reinfecting those who have previously recovered.
In the new research, published in the journal Nature, researchers assessed the effect of these mutations by developing a disabled, non-replicating virus—called a pseudovirus—to produce spike proteins on its surface.
They engineered pseudoviruses that had spike proteins along with the Omicron mutations as well as those found on the earliest variants identified during the pandemic.
The researchers assessed how well these different versions of the spike protein could bind to the ACE2 receptor—the protein on the surface of human cells which the virus uses as a door to enter and infect tissues.
They found that the Omicron spike protein could bind 2.4 times better than spike protein found in the virus isolated at the very beginning of the pandemic.
“That’s not a huge increase, but in the SARS outbreak in 2002-2003, mutations in the spike protein that increased affinity were associated with higher transmissibility and infectivity,” Dr Veesler noted.
When the scientists assessed how the immune system’s action against earlier isolates of the virus protected against Omicron, they found that antibodies from people who had been infected by earlier strains and from those who had received one of the six most-used vaccines currently available all had reduced ability to block infection.
To test this, the researchers used antibodies from patients who had previously been infected with earlier versions of the novel coronavirus, vaccinated against earlier strains of the virus, or had been infected and then vaccinated.
While antibodies from people who had been infected, recovered, and then took two doses of a Covid-19 vaccine also had reduced activity, the study found that this reduction in neutralising activity was less—about fivefold—suggesting that vaccination after infection is useful.
The scientists also found that all but one antibody treatments, currently authorised or approved to be used with patients exposed to the virus, had “no or had markedly reduced” activity against Omicron in the lab study.
The study also identified four classes of antibodies that retained their ability to neutralise Omicron.
Antibodies in each of these classes target one of four specific areas of the spike protein present in not only the Sars-CoV-2 variants but also a group of related coronaviruses, called sarbecoviruses.
The scientists believe these specific regions on the virus spike protein remain unchanged, and are “conserved,” indicating they play an essential function that the protein could lose if they mutated.
Based on the findings, the researchers say designing vaccines and antibody treatments targeting these regions could be effective against a broad spectrum of variants.