“The virus-like particle system allows us to quickly interrogate new variants and gain insight into whether their infectivity changes in cell culture,” said Dr. Melanie Ott, director of the Gladstone Institute of Virology and senior author of the new study. Say. “In the case of Omicron, it allows us to better grasp, at the molecular level, how this variant is different from others.”
“This method is very useful for rapidly studying the effectiveness of previous antibodies and vaccines against an emerging strain of virus,” noted Dr. Jennifer Doudna, the study’s other senior author, Glades. Senior Investigator at Qualcomm, a professor at the University of California, Berkeley, founder of the Institute for Innovative Genomics, and an investigator at the Howard Hughes Medical Institute.
A research team including Abdullah Saeed (left) and Alison Silling (right) used virus-like particles to determine which parts of the SARS-CoV-2 virus were responsible for its increased infectivity and transmissibility s reason. Source: Michael Short/Glaston Institute
Virus-like particles accelerate Omicron research
Epidemiological evidence suggests that the Omicron variant of SARS-CoV-2, first identified in South Africa in November 2021, spreads faster than the original strain of the virus. It also caused more breakthrough infections than other variants, such as in people who were previously infected or fully vaccinated against COVID-19.
To study the SARS-CoV-2 virus, Ott and Doudna’s research team created virus-like particles in the first few months of 2021. These particles are composed of the viral particle’s structural membrane, envelope, nucleotides and spike proteins. However, because virus-like particles do not have a viral genome, they cannot infect humans and are less dangerous to handle than live viruses. In addition, the researchers created new virus-like particles much faster than they could breed new live virus variants for analysis.
The researchers previously showed how the infectivity of the corresponding intact live virus correlates with the assembly effect of viroid particles. For example, according to cell culture experiments, if a viroid particle carrying a certain mutation is more efficient at producing virus particles, then a live copy of the virus with the same mutation is also more infectious.
Most recently, the team developed virus-like particles to capture the effects of different mutations in the emerging Omicron variant of SARS-CoV-2.
They found that Omicron mutations in the spike protein make virus-like particles twice as infective as particles with progenitor spike proteins. And virus-like particles carrying Omicron-mutated nucleocapsid proteins are 30 times more infective than the ancestor SARS-CoV-2.
“People have been looking at spike proteins, but we’ve seen in our system that for Delta and Omicron, the nucleocapsid is really more important in enhancing the transmission of this virus,” Ott said. I think if we want to generate Better vaccines or studies to stop the spread of COVID-19, we might want to consider targets other than spike proteins.”
When the team made virus-like particles carrying Omicron-mutated membrane or envelope proteins, they found that these particles were no more infectious than the ancestral virus-like particles; in fact, they were only about half as infectious as some other variants .
“Omicron has many mutations, and our findings tell us that some of these mutations are actually harmful to the virus,” said Abdullah Syed, first author of the study and a postdoc in Gladstone’s Doudna lab. “But it also means that if those brakes are lifted, Omicron has the potential to evolve to be more infectious.”
How Omicron Hides Antibodies
The researchers also tested the antibody’s ability to neutralize SARS-CoV-2 type particles, working with Curative’s innovation team, which has built a comprehensive serum biobank from more than 2 million vaccinations across the United States.
The team used sera from 38 people who had been vaccinated against COVID-19 or who had not but recovered from the virus, as well as sera from 8 people who had received a booster vaccine within the past 3 weeks. The researchers then exposed the virus-like particles they made to these serum samples to test their ability to neutralize the particles.
Serum from people who had been vaccinated with Pfizer/BioNTech or Moderna within the past 4 to 6 weeks showed high levels of neutralization of virus-like particles of ancestral SARS-CoV-2, but low levels of neutralization of particles of the Delta variant 3-fold and about 15-fold lower levels of neutralization against Omicron virus-like particles. People who received Johnson & Johnson’s vaccine or who recovered from COVID-19 had lower levels of neutralization of the ancestral virus-like particle, but not significantly different levels of neutralization of the Delta and Omicron variants.
In addition, the researchers showed that within 2 to 3 weeks of receiving a third dose of the Pfizer/BioNTech vaccine, all eight boosted people in the study had detectable levels of antibodies capable of neutralizing all SARS-CoV-2 variants , including Omicron. However, antibody levels against Omicron were still 8-fold lower than those against the ancestral virus.
“Our findings support the idea that Omicron is more capable of evading our vaccine-induced immunity than previous SARS-CoV-2 strains,” Ott said. “It also highlights that a booster shot of the mRNA vaccine appears to provide some A degree of extra protection, even for Omicron.”
Additionally, when the team tested the monoclonal antibodies casirivimab and imdevimab (commercially known as REGEN-Cov), they found that these drugs showed high levels of neutralization against the progenitor and Delta variants of SARS-CoV-2, but not the No neutralization was detected at all for Omicron-like particles.
“We’re certainly not at the point where we fully understand this variant, but our data add to the growing evidence that it appears to be very good at infection and very good at evading antibodies,” Syed said.