Washington: An international team of scientists have identified antibodies that neutralise Omicron and other SARS-CoV-2 variants. These antibodies target areas of the virus spike protein that remain essentially unchanged as the viruses mutate.
The Omicron variant has 37 mutations in the spike protein, which it uses to latch onto and invade cells. The highly unusually high number of mutations likely explain why the variant has been able to spread so rapidly, to infect people who have been vaccinated and to reinfect those who have previously been infected.
By identifying the targets of these “broadly neutralising” antibodies on the spike protein, it might be possible to design vaccines and antibody treatments that will be effective against not only the omicron variant but other variants that may emerge in the future, said David Veesler, an investigator with the Howard Hughes Medical Institute.
In the study, the team tested a larger panel of antibodies that had been generated against earlier versions of the virus, and identified four classes of antibodies that retained their ability to neutralise Omicron.
Members of each of these classes target one of four specific areas of the spike protein present in not only SARS-CoV-2 variants but also a group of related coronaviruses, called sarbecoviruses.
These sites on the protein may persist because they play an essential function that the protein would lose if they mutated. Such areas are called “conserved”.
The finding that antibodies are able to neutralise via recognition of conserved areas in so many different variants of the virus suggests that designing vaccines and antibody treatments that target these regions could be effective against a broad spectrum of variants that emerge through mutation, Veesler said.
“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,” said Veesler, Associate Professor of biochemistry at the University of Washington School of Medicine in Seattle. The findings were published in the journal Nature.
Further, the team also engineered a disabled, non-replicating virus, called a 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 on the earliest variants identified in the pandemic.
The team found that the Omicron variant spike protein (called the angiotensin converting enzyme-2 (ACE2) receptor) was able to bind 2.4 times better than spike protein found in the virus isolated at the very beginning of the pandemic.AA
“That’s not a huge increase,” Veesler noted, “but in the SARS outbreak in 2002-2003, mutations in the spike protein that increased affinity were associated with higher transmissibility and infectivity”.
They also found that the Omicron version was able to bind to mouse ACE2 receptors efficiently, suggesting Omicron might be able to “ping-pong” between humans and other mammals.
