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expert reaction to preprint looking at the Omicron variant and spike mediated immune escape, infectivity and cell-cell fusion

A preprint, an unpublished non-peer reviewed study, looks at SARS-CoV-2 Omicron spike mediated immune escape, infectivity and cell-cell fusion.


Prof Jonathan Ball, Professor of Molecular Virology, University of Nottingham, said:

“I’ve been very vociferous about over-interpreting the potential impact of spike mutations on biological behaviour until you have some hard data, and this paper goes some way to providing that. It highlights that mutations often work in tandem and mutation constellations that might be advantageous with respect to one property, for example antibody escape, might result in a fitness loss in some another aspect of virus infectivity. That makes desktop predictions of virus behaviour fraught with difficulties.

“What the paper shows nicely is that the spike protein from the Omicron variant was less sensitive to vaccine-induced antibody neutralisation, but this was restored to a large extent following a booster dose of vaccine – indeed our own and other studies have shown that increasing exposure to spike, through vaccination or natural infection, increases breadth of the antibody response to escape variants. This was why it was so important to have the booster programme, and I for one wished it had started earlier. 

“We must also remember that a more relevant measure of vaccines effectiveness is protection from disease, and waning antibody levels might result in susceptibility to infection, but there’s still a good deal of memory immunity in the tank to protect you from serious disease.

“The other major finding was that Omicron might infect lung cells less efficiently than those cells lining the nose and the throat. This is tantalising data that points towards the possibility that the virus is better adapted to the upper respiratory tract and less likely to infect the lung and therefore cause pneumonia, but this needs more thorough validation, especially as the level of omicron spike incorporation into the pseudoviruses appears less efficient than the other variants.

“We must always remember there are two facets to virus fitness. The virus’s own ability to infect and transmit, and the underlying immunity in the population in which it is trying to spread; it isn’t always easy to tease these apart. A virus circulating in a relatively immune population might appear less fit, than if it was introduced into a population that are immune-naive.”



All our previous output on this subject can be seen at this weblink:



Declared interests

Prof Jonathan Ball: “In receipt of funding to develop next-generation COVID-19 vaccines.”

None others received.

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