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New target for Covid-19 vaccines identified

Next generation vaccines for Covid-19 should aim to induce an immune response against ‘replication proteins’, essential for the very earliest stages of the viral cycle, according to a new study involving Queen Mary University of London researchers, Professor Aine McKnight, Dr Corinna Pade and Joseph Gibbons.

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Woman holds Covid-19 vaccine in hands. Credit: scaliger/iStock.com

Woman holds Covid-19 vaccine in hands. Credit: scaliger/iStock.com

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 at the very outset, thereby helping stop its spread.

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

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

Professor Áine McKnight, Professor of Viral Pathology at Queen Mary, said: "This is an important study giving us insight into the correlates of immune protection in a small proportion of the population. Still full vaccination is paramount."

Fundamental science discovery

This fundamental science discovery is borne from an observational study, COVIDsortium, which analysed the immune responses in a large cohort of London-based healthcare workers from the very start of the first UK pandemic wave.   

In a subset of healthcare workers, who showed no sign of SARS-CoV-2 infection (repeatedly testing negative by PCR and antibody tests) there was, however, 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 which generated T cells specific to SARS-CoV-2; compatible with this, the same individuals also had a low-level increase in another blood marker of viral infection.

Creating more effective vaccines

Senior author Professor Mala Maini (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.

“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.”

Next generation vaccines could also be developed to induce both memory T cells to target replication proteins and antibodies to target the spike protein.

This research was funded by the NIHR and UKRI’s UK Coronavirus Immunology Consortium.

The COVIDsortium is supported by funding donated by individuals, charitable Trusts, and corporations, with institutional support from Barts Health NHS Trust and Royal Free NHS Foundation Trust, in partnership with University College London and Queen Mary University London.

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