Worldwide, many groups are trying to develop vaccines that protect against a wide variety of coronaviruses and prevent a new pandemic. These efforts have now been bolstered by the discovery that some health professionals had pre-existing immunity to the SARS-CoV-2 virus during the first wave of the pandemic.
During the first half of 2020, around 700 health professionals in the UK were tested weekly as part of a crowdfunded study called COVIDsortium. Most of these people, who wore protective gear, never tested positive for Covid-19 in PCR tests or developed Covid-19 antibodies — proteins that bind to the outside of viruses and prevent cells from becoming infected.
However, when Leo Swadling and Mala Maini of University College London and their colleagues took a closer look, they found that some of those who tested negative had a protein in their blood linked to Covid-19 infection, as well as T-cell responses to the SARS. -CoV-2 virus. T cells are part of the immune system. It appears that these people had what Swadling calls an “abortion infection,” in which a strong, early T-cell response allowed them to get rid of the virus very quickly.
Virus-infected cells sound the alarm by displaying viral proteins on their surfaces, and T cells are the immune cells that learn to recognize these proteins and destroy infected cells. Crucially, while antibodies can only target proteins on the outside of a virus, T cells can learn to recognize viral proteins.
When the team looked at early blood samples from the people with failed infection, they found that even before they were exposed to SARS-CoV-2, they had some T cells that could recognize the proteins this virus uses to replicate itself. in infected cells.
The most likely explanation is that these people were often exposed to the existing human coronaviruses that cause about 10 percent of colds, Maini says. “We don’t know the historical infections of these individuals, so we don’t know for sure where the T cells come from,” she says.
Preventing another pandemic
The proteins involved in viral replication are very similar to SARS-CoV-2 and other human and animal coronaviruses, meaning that if vaccines can be developed that elicit a strong T-cell response against these proteins, they should protect against a very broad spectrum. range of coronaviruses – a so-called universal or pan-coronavirus vaccine. One way to do this would be to add mRNAs encoding these proteins to mRNA vaccines that target the virus’s external spike protein.
Adding additional components to next-generation coronavirus vaccines could protect against new variants that could develop as well as animal coronaviruses that could jump into humans and cause another pandemic, Swadling says. “There is a strong rationale for adding these proteins in addition to the spike protein,” he says.
Many groups are already trying to develop coronavirus vaccines that offer broader protection, says Olga Pleguezuelos of UK-based company SEEK. Her team has already created such a vaccine based on the most conserved parts of coronavirus proteins. “It’s only a matter of time before one of these members comes again [of the coronavirus family] causes an epidemic or pandemic,” she says. “If we end up with something as contagious as Covid and as deadly as MERS, we have a serious problem.”
However, it’s not clear how effective a vaccine that produces only a T-cell response would be, Maini says. Most vaccines work by stimulating an antibody response, although many also produce a T cell response.
Many groups are developing universal flu vaccines based on eliciting a T-cell response, but so far they have not proven very effective. Other teams are instead focusing on obtaining antibodies to parts of the flu virus’s outer viral proteins that don’t mutate. However, this doesn’t work with coronaviruses, says Peter Palese of the Icahn School of Medicine at Mount Sinai in New York. “They just don’t have a conserved region.”
Reference magazine: Nature, DOI: 10.1038/s41586-021-04186-8
More on these topics: