The omicron variant has proven not only to be the most transmissible of all variants of the SARS-CoV-2 coronavirus so far, but also the better able to evade the immune response of antibodies generated by vaccines and the infection itself. But it is possible that this ‘license to infect’ has its days numbered.
An international team of scientists has identified a group of antibodies that neutralize omicron and other variants of SARS-CoV-2. Such antibodies target areas of the virus peak protein that remain essentially unchanged as the viruses mutate. The results have been published in the journal
broadly neutralizing antibodies (capable of effectively neutralizing numerous different coronavirus strains) on the spike protein, it might be possible to design vaccines and antibody treatments that are effective not only against the omicron variant but also against other variants that may arise in the future.
“This finding tells us that by targeting antibodies that target highly conserved sites on the spike protein, there is a way to overcome the ongoing evolution of the virus,” explains David Veesler, researcher at the
Instituto Médico Howard Hughes and author of the study.
Veesler led the research project with Davide Corti of Humabs Biomed SA, Vir Biotechnology, in Switzerland.
The omicron variant has 37 mutations in the spike protein, which it uses to adhere to and invade cells. This is an unusually high number of mutations.
The researchers believe these changes partly explain why the variant has been able to spread so rapidly, being able to infect people who have been vaccinated and re-infect those who have already been infected.
“We have spent days trying to determine how this constellation of mutations in the omicron variant spike protein affects its ability to bind to cells and evade the antibody responses of the immune system,” says Veesler.
Veesler and his colleagues speculate that the large number of omicron mutations could have accumulated during a prolonged infection in a person with a weakened immune system or by the passage of the virus from humans to animal species and vice versa.
To evaluate the effect of these mutations, the researchers designed a virus without the ability to replicate, called pseudovirus, to produce spike proteins on its surface, as coronaviruses do. They then created pseudoviruses that had spike proteins with the omicron mutations and those found in the first variants identified in the pandemic.
They first looked at how different versions of the spike protein could bind to the protein on the surface of cells, which the virus uses to adhere to and enter the cell. This protein is called angiotensin converting enzyme 2 (ACE2) receptor..
Thus they discovered that the omicron variant spike protein could bind 2.4 times better than the spike protein found in the virus isolated at the beginning of the pandemic. Although this is not a very high increase, Veesler notes, “it should be noted that in the SARS outbreak in 2002-2003, mutations in the spike protein that increased affinity were associated with increased transmissibility and infectivity.”
The researchers also found that the omicron version could bind to mouse ACE2 receptors efficiently, suggesting that omicron might be able to interchange between humans and other mammals.
They then looked at how antibodies against earlier virus isolates protected against the omicron variant. They did it by using antibodies from patients who had previously been infected with earlier versions of the virus, vaccinated against previous strains of the virus or who had been infected and subsequently vaccinated.
They found that antibodies from people who had been infected by previous strains and from those who had received one of the six most-used vaccines currently available had a reduced ability to block infection.
Thus, for example, the antibodies of people who had been previously infected and those who had received the vaccines Sputnik V o Sinopharm, as well as a single dose of Janssen, had little or no ability to block or neutralize the entry of the omicron variant into cells.
However, the antibodies from people who had received two doses of the vaccines Moderna, Pfizer / BioNTech and AstraZeneca they retained some neutralizing activity, although they were reduced 20 to 40 times, much more than any other variant.
Finally, antibodies from people who had been infected, recovered and subsequently received two doses of vaccine also had reduced activity, but the reduction was less, approximately five times, clearly showing that vaccination after infection is useful.
Antibodies from people, in this case a group of patients on kidney dialysis, who had received a booster with a third dose of the vaccines de mRNAs produced by Moderna and Pfizer / BioNTech showed only a 4-fold reduction in neutralizing activity. «This shows that a third dose It’s really very useful against the omicron, ”says Veesler.
All but one antibody treatments, currently licensed or approved for use in patients exposed to the virus, lacked activity against omicron in the laboratory or had markedly reduced activity. The exception was sotrovimab, which had a two to three fold reduction in neutralizing activity.
But when they tested a larger panel of antibodies that had been raised against earlier versions of the virus, the researchers identified four classes of antibodies that retained their ability to neutralize omicron. Members of each of these classes target one of four specific areas of the spike protein present not only in SARS-CoV-2 variants, but also in a group of related coronaviruses, called sarbecoviruses. These sites on the protein may persist because they perform an essential function that the protein would lose if mutated. These areas are called ‘conserved’.
The finding that antibodies can neutralize by recognizing conserved areas in so many different variants of the virus suggests that the design of vaccines and antibody treatments that target these regions could be effective against a broad spectrum of variants arising across mutation, Veesler concludes.