COVID immunity inspires the next generation of vaccines

COVID immunity inspires the next generation of vaccines
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University College London (UCL) research suggests that COVID immunity could help develop the next generation of COVID-19 vaccines by inducing an immune response against ‘replication proteins’ essential for the early stages of the viral cycle.

Researchers say that the discovery, published in Nature, could lead to the creation of a pan-coronaviruses vaccine using cells activated by COVID immunity that not only protects against SARS-CoV-2 and its variants but also against coronaviruses that cause common colds and animal coronaviruses.

This approach could work in conjunction with the current vaccine offering in the UK, which only triggers immune responses to the spike protein that protrudes from the outside of the virus.

Analysing COVID immunity of some London based healthcare workers

The concept is that by designing vaccines that activate immune memory cells, known as T cells, to attack infected cells expressing this part of the virus’s internal machinery, it may be possible to eliminate SARS-CoV-2 and stop its spread.

For the hospital-led observation study, COVIDsortium from UCL and St Bartholomew analysed COVID immunity responses of a large cohort of London-based healthcare workers from the beginning of the first UK pandemic wave.

A cluster of healthcare workers who showed no sign of SARS-CoV-2 infection, measured by repeatedly testing negative by PCR and antibody tests, did show an increase in T cells. However, they had not avoided infection entirely; the healthcare workers appeared to have experienced a transient low-level (abortive) infection not detectable by routine tests. They had generated T cells specific to SARS-CoV-2 and demonstrated a low-level increase in another blood marker of the viral infection.

Professor Mala Maini, the senior author of the study from UCL 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.”

This highlighted that a select group of healthcare workers, despite the likely exposure to the virus, had been able to naturally clear the virus before it became detectable by routine tests. Researchers intensively monitored the healthcare workers for a sign of infection and immune responses; however, they identified a minority with the SARS-CoV-2 specific T cell response.

How can some individuals clear the infection better than others?

Lead author, Dr Leo Swadling from UCL Infection & Immunity, commented: “It could be due to the infection history of these individuals. The health care 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.”

The study found that individuals with pre-existing T cells may have them because of previous exposure to other coronaviruses like the common cold. This gives certain people a head start against COVID-19, favouring their immune system eliminating the virus before it replicates.

Creating a vaccine that activates immune memory cells

The researchers express that the next generation of COVID vaccines could be developed to induce both memory T cells to target replication proteins and antibodies to target the spike protein.

Professor Maini commented: “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’ 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.”


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