T cells fit to tackle Omicron, suggests new study

A transmission electron micrograph of negative-stained SARS-CoV-2 Omicron variant virions, false-coloured. Image: Dr Jason A. Roberts, Head of Electron Microscopy and Structural Virology at The Royal Melbourne Hospital’s Victorian Infectious Diseases Reference Laboratory, Doherty Institute

Research from the University of Melbourne and Hong Kong University of Science and Technology (HKUST) has revealed T cells, one of the body’s key defences against COVID-19, are expected to be effective in mounting an immune response against Omicron despite its significantly higher mutations compared to previous variants of concern.

T cells, generated both by vaccinations and COVID-19 infections, have been shown to be critical in limiting progression to severe disease by eliminating virus-infected cells and helping with other immune system functions.

Preliminary studies have reported that Omicron (fast becoming the most dominant circulating strain globally) can escape antibodies produced by vaccination or natural COVID-19 infection, raising concerns about the increased possibility of reinfection and breakthrough cases.

Published in Viruses, the team analysed over 1,500 fragments of SARS-CoV-2’s viral proteins, called epitopes, that have been found to be recognised by T cells in recovered COVID-19 patients or after vaccination. The team’s findings suggest Omicron is unlikely to be able to evade T cells, adding to a growing body of evidence from research groups around the world who are also investigating T cell responses to COVID-19.

“Despite being a preliminary study, we believe this is positive news. Even if Omicron, or some other variant for that matter, can potentially escape antibodies, a robust T cell response can still be expected to offer protection and help to prevent significant illness,” University of Melbourne Professor Matthew McKay, who co-led the research said.

The most concerning aspect of Omicron is the abundance of mutations in its spike protein, which is the primary target of COVID-19 vaccines.

The spike enables the virus to attach and enter cells in humans. Current vaccines induce neutralising antibodies aimed at blocking this process, however these antibodies have been reported to be less effective against Omicron compared with previous variants, like Delta.

In analysing virus epitopes from the spike protein that are targeted by T cells in vaccinated or previously infected individuals, the study found that only 20 per cent showed mutations associated with Omicron.

Even then, these mutations do not necessarily mean the virus will be able to evade the body’s T cells.

“Among these T cell epitopes that have Omicron mutations, our further analysis revealed that more than half are predicted to still be visible to T cells. This further diminishes the chance that Omicron may escape T cells’ defences,” HKUST Research Assistant Professor and study co-lead, Professor Ahmed Abdul Quadeer said.

While the study focused on the spike protein of the virus, when the team broadened their analysis to other virus proteins, they found an overwhelming majority (more than 97 per cent) of non-spike T cell epitopes do not encompass mutations associated with Omicron.

“These results overall, would suggest that broad escape from T cells is very unlikely,” Professor McKay said.

“Based on our data, we anticipate that T cell responses elicited by vaccines and boosters, for example, will continue to help protect against Omicron, as observed for other variants.  We believe this presents some positive news in the global fight against Omicron.”