In a new study from UCL Infection & Immunity, researchers found 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.
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.
The discovery 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 new emerging animal coronaviruses.
In the study, the team analyzed 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.
By intensively monitoring health care workers for signs of infection and immune responses, the team identified a minority with this particular SARS-CoV-2 specific T cell response.
The 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.
The team says a vaccine that can induce T cells to recognize 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 recognize other coronaviruses that currently infect humans or that could in the future.
The next-generation vaccines could be developed to induce both memory T cells to target replication proteins and antibodies to target the spike protein.
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The study is published in Nature. One author of the study is Professor Mala Maini.
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