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Robust T Cell Responses Are Equipped to Tackle Omicron

A robust T cell response can be expected to offer protection and help to prevent severe disease caused by Omicron.

Since it was first detected in Botswana, South Africa, and Hong Kong in November 2021, Omicron has been rapidly emerging to become the most dominant circulating strain of SARS-CoV-2 globally. On 25 December 2021, genomic data from Global Initiative on Sharing All Influenza Data (GISAID), a global science initiative and primary source that provides open access to genomic data of influenza viruses and the coronavirus responsible for the COVID-19 pandemic, revealed that Omicron has been detected in at least 85 countries. According to scientists, the greatest concern with regards to Omicron is the abundance of mutations in its spike protein – some found in previous variants of concern and some others new. Since the spike protein serves as the primary target of COVID-19 vaccines, these mutations could significantly undermine the neutralising capacity of antibodies mounted from vaccines and previous infections. Studies have also shown that these antibodies are less effective against Omicron compared to previous variants such as Delta, thereby raising concerns about the increased threat of reinfection and breakthrough cases.

Fortunately, researchers from the Hong Kong University of Science and Technology (HKUST) and the University of Melbourne have reported that T cells, one of the body’s key defences against COVID-19, may be effective in building immune response against Omicron. By analysing more than 1,500 fragments of SARS-CoV-2’s epitopes that have been identified to be recognisable by T cells in recovered patients or post-vaccinated individuals, the team’s findings indicate that Omicron is unlikely to be able to evade T cells, potentially allowing T cells to help limit severe illness in infected individuals.

“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,” said Professor Matthew McKay from the University of Melbourne, who co-led the research.

T cell responses generally act as a key defence mechanism against viral infections by helping to activate antibody-producing B cells and removing virus-infected cells. Although the T cell response to COVID-19 infection has not been researched as closely as antibodies, T cell responses have been linked to rapid viral clearance and limited progression to severe disease, even with reduced or absent neutralising antibody response.

To clarify the role of T cell responses, the researchers examined more than 1,500 virus epitopes that are derived from the SARS-CoV-2 spike protein and are known to be targeted in COVID-19 infected and/or vaccinated individuals. They were also keen to determine how Omicron’s mutations interfere with the ability of T cells to bind to epitopes. Their investigation revealed that only around 20 per cent of the virus epitopes exhibited Omicron-associated mutations, though this does not necessarily mean that 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,” explained study co-lead Professor Ahmed Abdul QUADEER, Research Assistant Professor at HKUST’s Department of Electronic and Computer Engineering.

Besides the mutations on the spike protein, the team extended their analysis to other virus proteins and discovered that more than 97 per cent of non-spike T cell epitopes did not exhibit Omicron-associated mutations.

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

The team’s findings bring hope that robust T cell immunity may offer a high level of protection against severe disease, potentially reducing the risk of hospitalisation and death. Nonetheless, the researchers cautioned that T cell responses alone are insufficient to block infection and prevent transmission and there may be other epitopes that they are unaware of. According to the study, further targeted experiments will be needed to validate the robustness of T cell responses against Omicron and to test the capacity of specific epitope mutations to enable T cell escape. [APBN]

Source: Ahmed et al. (2022). SARS-CoV-2 T Cell Responses Elicited by COVID-19 Vaccines or Infection Are Expected to Remain Robust against Omicron. Viruses, 14(1), 79.