Next-generation COVID-19 vaccines could aim to induce an immune response against replication proteins to stop the virus in its tracks at the earliest stages, researchers have said.
A new study by academics at UCL, UK, which was published last night, said vaccines that activate T cells could eliminate SARS-CoV-2 at the very outset, which would help to stop its spread.
Writing in the latest edition of Nature, the authors say it could complement currently licensed COVID-19 vaccines, which only trigger immune responses to the spike protein, and could lead to the creation of a pan-coronaviruses vaccine, which protects against SARS-CoV-2 and its variants as well as coronaviruses that cause common colds, and to new emerging animal coronaviruses.
Senior author Professor Mala Maini, of 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.”
She said if T cells recognised the virus’ replication machinery it would add another layer of protection to that provided by the spike-focused immunity, which is generated by the current vaccines.
A dual-action vaccine would provide more flexibility against mutations and could also provide longer-lasting immunity. Added Prof Maini.
The research was undertaken as part of COVIDsortium, a UCL and St Bartholomew’s Hospital-led observational study that analysed the immune responses in a large cohort of London healthcare workers from the start of the first UK wave of the pandemic in March 2020.
They found there was a subset of healthcare workers who showed no sign of SARS-CoV-2 infection – and repeatedly tested negative by PCR and antibody tests – but had an increase in T cells.
The researchers say this subset experienced a transient low-level infection that was not detectable by routine tests, but which generated T cells specific to SARS-CoV-2. They also had a low-level increase in another blood marker of viral infection.
Lead author Dr Leo Swadling, of UCL 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.”
Swadling L, Diniz MO, Schmidt NM et al. Pre-existing polymerase-specific T cells expand in abortive seronegative SARS-CoV-2. Nature 11 November 2021; doi: 10.1038/s41586-021-04186-8
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