T cells take the fight to Omicron

University of Cape Town (UCT) researchers led an important new study published on 31 January 2022 in the prestigious scientific journal Nature. The publication, titled “T cell responses to SARS-CoV-2 spike cross-recognize Omicron”, shows that while the Omicron variant of SARS-CoV-2 can escape neutralisation by antibodies, it is not able to evade cellular immune responses.

On 26 November 2021 the newest SARS-CoV-2 variant, later designated Omicron, was described. Compared with the original virus, Omicron has over 30 mutations in the RNA sequence that codes for its spike protein (the protein that allows the virus to infect the body’s cells). Because antibodies target this spike protein, by changing the protein these mutations enable the virus to escape the neutralising effect of antibodies the body has produced during previous infection or as a result of vaccination.

The human adaptive immune response is broadly comprised of B and T cells; B cells produce antibodies, while T cells directly (CD8+) or indirectly (CD4+) participate in clearing infections. While antibody levels may be quick to rise – and fall – following infection, the T cell response is slower to initiate, but more durable.

Important questions

Would T cells generated in response to previous COVID-19 infection or vaccination recognise Omicron? Or is Omicron so different to previous SARS-CoV-2 variants that the immune system needs to start from scratch? These were some of the important questions investigated in this study.

Study co-leads Dr Catherine Riou and Associate Professor Wendy Burgers collaborated with a large team whose connections span South Africa and the globe to answer these questions. Researchers from the Africa Health Research Institute, the University of KwaZulu-Natal, the National Health Laboratory Service, the University of the Witwatersrand, the University of Pretoria, the University of California San Diego, the South African Medical Research Council, and Stellenbosch University, among others, participated.

“The world was looking for answers – would vaccines still be effective against Omicron?”

Within UCT, the team included members of the Institute of Infectious Disease and Molecular Medicine (IDM), the Wellcome Centre for Infectious Diseases Research in Africa and the Desmond Tutu HIV Centre hosted at the IDM, as well as the Faculty of Health Sciences’ Department of Medicine.

“We knew that we needed to answer this question as quickly as possible. The world was looking for answers – would vaccines still be effective against Omicron?” said first author of the paper, Dr Roanne Keeton.

“We pulled together our many collaborators from around the country to make this study possible, and literally worked night and day, seven days a week, to perform this research.”

T cells resilient in the face of a changed virus

The researchers found that both vaccination and COVID-19 infection induced T cell responses. However, both CD4+ and CD8+ T cell responses were lower in Omicron cases than in patients who had the original SARS-CoV-2 virus. Despite this, CD4+ and CD8+ T cell recognition of Omicron is largely preserved. This means that despite the changes in the spike structure from the original virus variant to Omicron, T cells were still able to recognise and respond to it.

“The second line of defence – T cells – can still recognise Omicron if you have been vaccinated or had COVID-19 previously. This is good news – its likely T cells that are keeping people out of hospital in this wave,” said Associate Professor Burgers.

“We looked at whether T cells from patients with Omicron infection made a similar response as patients infected with other variants from previous waves.”

In addition to extensive mutations in the spike protein, Omicron has 20 additional mutations in other proteins which could potentially enable it to evade T cells. However, the researchers found that these other mutations do not significantly affect a person’s ability to make a T cell response to Omicron after infection.

“We looked at whether T cells from patients with Omicron infection made a similar response as patients infected with other variants from previous waves – the original virus, beta and delta variants,” said Dr Riou.

“As far as the T cells are concerned, Omicron induces a similar immune response as other variants of concern, showing that T cells are recognising portions of the virus that haven’t changed over time,” Riou added.

Neutralising antibodies are not the only immune molecules of importance in the body’s internal war against SARS-CoV-2. While these short-lived and specific molecules lead the charge into battle, T cells’ durable, broad and inescapable attacks might prove the ultimate responders said Keeton.