Antibodies capable of blocking the identified Omicron mutants

Scientists have identified antibodies that neutralize Omicron And other variants coronavirus By targeting areas that are essentially unchanged when the virus mutates.

This study, published in Nature, may help design vaccines and antibody therapies that are effective not only against Omicron, but also against other mutants that may emerge in the future.

“This finding shows that there is a way to overcome the continued evolution of the virus by focusing on antibodies that target these highly conserved sites of the spike protein,” said the University of Washington School of Medicine. Said David Veesler, an associate professor at the University of Washington. America.

Omicron variants carry an unusually large number of 37 mutations in the peplomer used by the virus to invade and infect human cells.

These changes are believed to explain some of the reasons why the mutants spread so rapidly that they could infect vaccinated people and re-infect previously infected people. increase.

“The main question we were trying to answer was how this series of mutations in the peacular mutant spike protein affected the ability of the immune system to bind to cells and evade antibody responses. We did, “said Veesler.

To assess the effects of these mutations, researchers designed a defective non-replicating virus, called a pseudovirus, to produce peplomers on its surface, similar to the coronavirus.

They then created a pseudovirus containing a peaplomer with the Omicron mutation and one found in the earliest variant identified in the pandemic.

Researchers first looked at how well different versions of peplomers can bind to cell surface proteins. It is used by the virus to latch and invade cells. This protein is called the angiotensin converting enzyme 2 (ACE2) receptor.

They found that the Omicron mutant peplomer could bind 2.4 times better than the peplomer found in the first isolated virus of the pandemic.

“This is not a big increase, but in the 2002-2003 SARS outbreak, peplomer mutations with increased affinity were associated with higher infectivity and infectivity,” Veesler said. I am.

They also found that the Omicron version was able to efficiently bind to the mouse ACE2 receptor. This suggests that Omicron may be able to “ping pong” between humans and other mammals.

Next, researchers investigated how well antibodies against early isolates of the virus were protected against Omicron variants.

They did this using antibodies from patients who were previously infected with a previous version of the virus, vaccinated against a previous strain of the virus, or were infected and then vaccinated.

The team found that all antibodies from people infected with previous strains and those who received one of the six most used vaccines currently available have a reduced ability to stop the infection. did.

Antibodies in people who were infected, recovered, and vaccinated twice also had decreased activity, but the decrease was as low as about 5 times, clearly showing that post-infection vaccination is useful.

Antibodies from a group of people who received boost immunization on a third dose of the mRNA vaccine produced by Moderna and Pfizer, in this case renal dialysis patients, showed a reduction in neutralization activity by only a quarter. ..

“This shows that the third dose really really helps Omicron,” Veesler said.

All antibody treatments, except one that is currently approved or approved for use in patients exposed to the virus, had no or significantly reduced activity against Omicron in the laboratory.

The exception is an antibody called sotrovimab, which has a 2- to 3-fold reduction in neutralizing activity, the researchers said.

However, when testing a larger panel of antibodies produced against previous versions of the virus, researchers identified four classes of antibodies that retain the ability to neutralize Omicron.

Members of each of these classes target one of four specific regions of the spike protein that is present not only in the SARS-CoV-2 mutant, but also in a group of related coronaviruses called salvecoviruses. ..

These sites on the protein may survive because they play an important role in the loss of the protein when mutated. Such areas are called “saved”.

The discovery that antibodies can be neutralized through recognition of conserved regions of so many different variants of the virus is effective for a wide range of variants in the design of vaccines and antibody therapies targeting these regions. It suggests a possibility, Veesler added.