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Omicron better at evading vaccine-induced antibodies but may cause less severe lung disease, say University of Cambridge researchers

University of Cambridge researchers have found that the Omicron variant of the Covid-19 virus appears to be significantly better than previous variants at evading vaccine-induced antibodies, but early data suggests it is less likely to cause severe illness in the lungs.

They found Omicron required about a 10-fold increase in the concentration of serum antibody to neutralise the virus, compared to the Delta variant.

An illustration of the Omicron (B. 1. 1. 529) variant of the Covid-19 virus, showing the spike protein mutations. Image: COG-UK Mutation Explorer
An illustration of the Omicron (B. 1. 1. 529) variant of the Covid-19 virus, showing the spike protein mutations. Image: COG-UK Mutation Explorer

Antibodies from the majority of individuals in the study who had received two doses of the AstraZeneca vaccine were unable to neutralise the virus

However, following a third dose of the Pfizer vaccine, both groups saw a significant increase in neutralisation, underscoring the importance of the booster roll-out.

And they found that Omicron was less efficient at entering cells and causing fusion between cells, suggesting it may be less likely to cause severe lung disease.

For the study, the researchers, led by Professor Ravi Gupta at the Cambridge Institute of Therapeutic Immunology and Infectious Disease, worked in secure conditions to create synthetic viruses, known as ‘pseudoviruses’, that carried key mutations from the Delta and Omicron strains of SARS-CoV-2.

There have been concerns that the large number of mutations in Omicron - which first emerged in South Africa and is also known as B.1.1.529 - means existing vaccines will be less effective at protecting against infection and illness.

Working with collaborators from Japan, including Dr Kei Sato of the University of Tokyo, the researchers tested the pseudoviruses against blood samples donated to the NIHR Covid-19 BioResource. The blood samples were from vaccinated individuals who had received two doses of either the AstraZeneca (ChAdOx-1) or Pfizer (BNT162b2) vaccines.

Professor Gupta said: “The Omicron variant appears to be much better than Delta at evading neutralising antibodies in individuals who have received just two doses of the vaccine. A third dose ‘booster’ with the Pfizer vaccine was able to overturn this in the short term, though we’d still expect a waning in immunity to occur over time.”

Spike proteins on the surface of SARS-CoV-2 bind to a protein receptor, known as ACE2, on the surface of cells in the lung. Both the spike protein and ACE2 are then cleaved, which allows genetic material from the virus to enter the host cell.

The virus manipulates the host cell’s machinery, enabling it to replicate and spread.

Prof Ravi Gupta. Picture: Homerton College
Prof Ravi Gupta. Picture: Homerton College

The researchers used their pseudoviruses to infect cells in lung organoids, which are like ‘mini-lungs’ modelling parts of the lung.

Omicron has three mutations that were predicted to favour the spike cleavage,but the researchers found that the Omicron spike protein was less efficient than Delta’s at cleaving the ACE2 receptor and entering the lung cells.

Once in cells, it was also less able than Delta to cause fusion between cells, which is a phenomenon associated with impaired cell-to-cell spread.

Respiratory tissues taken following severe disease often feature fused cells.

When the team used a live Omicron virus and compared it to Delta in a spreading infection experiment using lung cells, they found Omicron was significantly poorer in replication. This confirmed the findings on impaired entry.

Prof Gupta added: “We speculate that the more efficient the virus is at infecting our cells, the more severe the disease might be. The fact that Omicron is not so good at entering lung cells and that it causes fewer fused cells with lower infection levels in the lab suggests this new variant may cause less severe lung-associated disease.

“While further work is needed to corroborate these findings, overall, it suggests that Omicron’s mutations present the virus with a double-edged sword: it’s got better at evading the immune system, but it might have lost some of its ability to cause severe disease.”

But Prof Gupta warned: “Omicron still represents a major public health challenge. Individuals who have only received two doses of the vaccine – or worse, none at all – are still at significant risk of Covid-19, and some will develop severe disease.

“The sheer number of new cases we are seeing every day reinforces the need for everyone to get their boosters as quickly as possible.”

The research was supported by Wellcome and the NIHR Cambridge Biomedical Research Centre.

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