Scientists have identified antibodies that can neutralize Omicron and other SARS-CoV-2 variants

An international team of scientists has identified an antibody rapid test that can neutralize Omicron and other SARS-CoV-2 variants. These antibodies target areas of the virus spike protein, which remain basically unchanged as the virus mutates. David Veesler, an investigator at the Howard Hughes Medical Institute and associate professor of biochemistry at the University of Washington School of Medicine in Seattle, said that by identifying the targets of these "widely neutralizing" antibodies on spike proteins, it may be possible to design variants not only for Omicron but also for the future. There may be other variants of effective vaccines and antibody therapies. "

This finding tells us that by focusing on antibodies against these highly conserved sites on spike proteins, there is a way to overcome the continued evolution of viruses.

Veesler and Davide Corti of Humabs Biomed SA, a Swiss Vir biotechnology company, led the research project. The results of the study were published in the journal Nature on December 23. The lead authors of the study are Elisabetta Cameroni and Christian Saliba (Humabs), John E. Bowen (University of Washington Biochemistry) and Laura Rosen (Vir).

The Omicron variant has 37 mutations in the spike protein, and it uses these mutations to lock and invade cells. This is an abnormally high number of mutations. It is believed that these changes partly explain why the variant can spread so quickly, infecting people who have been vaccinated, and reinfecting those who have been previously infected. The main question the researchers are trying to answer is: How does this combination of mutations in the spike protein of the Omicron variant affect its ability to bind to cells and evade the immune system’s antibody response,"

Veesler and his colleagues speculate that a large number of Omicron mutations may have accumulated during long-term infections in people with weakened immune systems, or that the virus jumped from humans to animal species and back.

In order to evaluate the impact of these mutations, the researchers designed a virus that cannot replicate, called a pseudovirus, which produces spike-like proteins on its surface. Just like coronaviruses, the spike proteins of these pseudoviruses have Omicron mutations and those in large Mutations found on the earliest variants discovered in an epidemic.

The researchers first observed the extent to which different versions of spike proteins can bind to proteins on the cell surface, which viruses use to grab and enter cells. This protein is called angiotensin-converting enzyme-2 (ACE2) receptor.

They found that the Omicron variant spike protein can bind 2.4 times stronger than the spike protein found in viruses isolated at the beginning of the pandemic. "This is not a huge increase," Veesler pointed out. "But in the SARS outbreak in 2002-2003, mutations in the spike protein that increased the affinity were associated with higher transmission and infectivity." They also found the Omicron version. The ability to effectively bind to the mouse ACE2 receptor indicates that Omicron may be able to communicate between humans and other mammals."

The researchers then examined the degree to which antibodies against the early isolates of the virus protect the Omicron variant. They achieve this goal by using antibodies from patients who have previously been infected with an early version of the virus, or vaccinated against an early strain of the virus, or from patients who have been vaccinated after infection.

They found that antibodies in people who had been infected by the early virus strains and people who had been vaccinated with one of the six most commonly used vaccines reduced their ability to stop infection.

Antibodies from previously infected people and those who have been vaccinated with Sputnik V (Russian satellite) or a single dose of Johnson & Johnson vaccine have little ability to prevent-or "neutralize"-the Omicron variant from entering the cell. The antibodies of people who received two doses of Moderna, Pfizer/BioNTech and AstraZeneca vaccine retained some neutralizing activity, although it was reduced by 20 to 40 times, which is worse than dealing with any other variant.

The antibody activity of people who recovered from the infection and then received two doses of the vaccine also had a decrease in antibody activity, but the decrease was small, about 5 times. This observation clearly shows that vaccination after infection is useful.

In this case, the neutralizing activity of a group of kidney dialysis patients' antibodies after receiving the third dose of Moderna and the mRNA vaccine produced by Pfizer/BioNTech was only reduced by 4 times. "Veesler said: "This shows that the third dose of vaccine is really helpful in preventing Omicron infection.

Except for one antibody treatment method currently authorized or approved for patients exposed to the virus, all other antibody treatment methods have no activity or significantly reduced activity against Omega in the laboratory. The study found that an antibody called sotrovimab, its neutralizing activity was reduced by 2 to 3 times.

But when they tested a larger panel of antibodies produced against an earlier version of the virus, the researchers found that four types of antibodies retained the ability to neutralize Omicron. Each member of these categories targets one of four specific regions of spike protein, which are not only present in the SARS-CoV-2 variant, but also in a group of related coronaviruses, the Sabeko virus. These sites on the protein may persist because they perform an important function, and if they are mutated, the protein will lose this function.

Veesler said that the discovery that antibodies can neutralize by recognizing conserved regions in so many different virus variants suggests that designing vaccines and antibody treatments that target these regions may be effective for a wide range of variants that emerge through mutation.