Covid-resistant people point way to universal coronavirus vaccine

Illustration of a T-cell that targets SARS-CoV-2 particles JUAN GERTNER/SCIENCEPHOTO LIBRARY
Many organizations around the world are working to develop vaccines that can protect against many coronaviruses, and help prevent another pandemic. This effort has been further aided by the discovery of pre-existing immunity to SARS-CoV-2 virus in some healthcare workers during the initial wave of the pandemic.

In the first half 2020, approximately 700 UK healthcare workers were tested weekly in a crowdfunded study called COVIDsortium. These people, most of whom wore protective gear, did not test positive for covid-19 in PCR or develop covid-19 antibodies - proteins which bind to viruses and prevent cells from becoming infected.

Leo Swadling at University College London and Mala Maini, a University College London researcher, looked closer and found that some people who had tested negative for covid-19 were also positive for T cell responses to the SARS/CoV-2 virus. T cells are an important part of the immune system. Swadling describes this as an "abortive infected", which Swadling says was a condition where the immune system activated quickly to eliminate the virus.

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Infected cells emit a warning by displaying virus proteins on their surfaces. T cells are immune cells that recognize these proteins and can destroy infected cells. Importantly, although antibodies cannot target viruses on the outside, T cells are able to recognize any virus proteins.

The team examined blood samples taken from people with an abortive infection and found that they had T cells that could recognize the proteins this virus uses to reproduce inside infected cells.

Maini believes that the most plausible explanation is that the people in question were exposed to human coronaviruses which cause approximately 10% of all colds. She says, "We don’t know the history of these people so we don’t know where the T cells are coming."

Preventing another pandemic

SARS-CoV-2, and other coronaviruses in animals and humans, has very similar proteins. This means that vaccines that can elicit strong T cells responses against these proteins should be able to protect against a wide range of coronaviruses. A so-called universal vaccine or pan-coronavirus vaccine is possible. This could be done by adding mRNAs that code for these proteins into mRNA vaccines which target the virus's external spike.

Swadling says that adding additional components to the next generation coronavirus vaccines could protect against new variants and animal coronaviruses, which could spread into humans and cause a pandemic. He says that there is strong evidence for including these proteins in the vaccine along with the spike protein.

Many groups are currently working on coronavirus vaccines with greater protection. Olga Pleguezuelos, UK-based company SEEK, said that many of these vaccines are being developed. This vaccine was developed by her team using the most preserved coronavirus proteins. She says, "It's only a matter of time until another member of the coronavirus family creates an epidemic. "If we have something as deadly as MERS and as infectious as covid, we're in serious trouble."

Maini states that it's not clear how effective a vaccine which only stimulates a T-cell response would be. Although most vaccines stimulate an antibody response, many also trigger a T-cell response.

Although many groups have been working on universal flu vaccines that elicit a T-cell response, these have not proven to be very effective. Others are focusing their efforts on developing antibodies that target the parts of the virus' outer viral proteins that don’t mutate. Peter Palese, from the Icahn School of Medicine in Mount Sinai, New York, states that this will not work for coronaviruses. They don't have a preserved region.

Journal reference: Nature, DOI: 10.1038/s41586-021-04186-8