Researchers identify new target for Covid-19 vaccines

Past exposure to other coronaviruses may speed up the clearance of Covid-19, a study has suggested.

Researchers say the next generation of Covid vaccines should aim to induce an immune response against specific proteins that are essential for the earliest stages of the viral cycle.

By designing jabs that activate immune memory cells, known as T cells, to attack infected cells, it may be possible to eliminate Covid at the start, helping to stop its spread, the study suggested.

This could complement Covid-19 vaccines currently licensed in the UK, which only trigger immune responses to the spike protein that protrudes from the outside of the virus.

Researchers said the discovery, published in the Nature journal, could lead to the creation of a vaccine for all coronaviruses.

This would not only protect against Covid and its variants, but also against coronaviruses that cause common colds and new emerging animal coronaviruses.

Senior author Professor Mala Maini, of UCL Division of Infection & Immunity, said: “Our research shows that individuals who naturally resisted detectable Sars-CoV-2 infection generated memory T cells that target infected cells expressing the replication proteins, part of the virus’s internal machinery.

“These proteins – required for the earliest stage of the virus’s life cycle, as soon as it enters a cell – are common to all coronaviruses and remain ‘highly conserved’, so are unlikely to change or mutate.

“A vaccine that can induce T cells to recognise and target infected cells expressing these proteins, essential to the virus’s success, would be more effective at eliminating early Sars-CoV-2, and may have the added benefit that they also recognise other coronaviruses that currently infect humans or that could in the future.

“T cells recognising the virus’s replication machinery would provide an additional layer of protection to that provided by the spike-focused immunity that is generated by the already highly efficacious current vaccines.

“This dual-action vaccine would provide more flexibility against mutations, and because T cells can be incredibly long-lived, could also provide longer-lasting immunity.

“By expanding pre-existing T cells, such vaccines could help to stop the virus in its tracks at a very early stage.”

A UCL and St Bartholomew’s Hospital-led observational study, COVIDsortium, analysed the immune responses of London-based healthcare workers from the start of the first wave of the pandemic in the UK.

In a subset of healthcare workers who showed no sign of Covid infection – repeatedly testing negative – there was an increase in T cells.

Rather than having avoided infection completely, a subset of healthcare workers appear to have experienced a transient low-level (abortive) infection, not detectable by routine tests.

But it generated T cells specific to Covid – compatible with this, the same individuals also had a low-level increase in another blood marker of viral infection.

Lead author, Dr Leo Swadling, of UCL Division of Infection & Immunity, said: “We know that some individuals remain uninfected despite having likely exposure to the virus.

“What we didn’t know is whether these individuals really did manage to completely avoid the virus or whether they naturally cleared the virus before it was detectable by routine tests.

“By intensively monitoring health care workers for signs of infection and immune responses, we identified a minority with this particular SARS-CoV-2 specific T cell response.

“What is really informative is that the T cells detected in these individuals, where the virus failed to establish a successful infection, preferentially target different regions of the virus to those seen after infection.”

Commenting on why some people might be able to clear an infection better than others, he added: “It could be due to the infection history of these individuals.

“The healthcare workers that were able to control the virus before it was detectable were more likely to have these T cells that recognise the internal machinery before the start of the pandemic.

“These pre-existing T cells are poised ready to recognise Sars-CoV-2.”

Explaining where these pre-existing T cells come from, Dr Swadling continued: “The regions of the virus that these T cells recognise are highly conserved amongst other members of the coronavirus family, such as those that cause common colds every year.

“Previous common cold exposure may have given these individuals a head start against the virus, tipping the balance in favour of their immune system eliminating the virus before it could start to replicate.”

This research was funded by the National Institute for Health Research and UK Research and Innovation’s UK Coronavirus Immunology Consortium.