The T cells of the common cold cross-protect against SARS-CoV-2 infection

People with higher levels of common cold coronavirus T cells are less likely to be infected with SARS-CoV-2.

A new study, published in Nature Communications and led by researchers from Imperial College London, provides the first evidence of a protective role for these T cells. While previous studies have shown that other coronavirus-induced T cells can recognize SARS- CoV-2, the new study examines for the first time how the presence of these T cells at the time of exposure to SARS-CoV-2 affects whether someone becomes infected.

The researchers also say their findings provide a blueprint for a second-generation universal vaccine that could prevent infection with current and future variants of SARS-CoV-2, including Omicron.

Dr Rhia Kundu, first author of the study, of the Imperial's National Heart & Lung Institute, says, “Being exposed to the SARS-CoV-2 virus doesn't always cause an infection and we were anxious to understand why. We found that high levels of pre-existing T cells, created by the body when infected with other human coronaviruses such as the common cold, can protect against COVID-19 infection.

“While this is an important discovery, it is only a form of protection, and I stress that no one should rely on that alone. Instead, the best way to protect yourself from COVID-19 is to be fully vaccinated, including getting the booster dose. "

The study started in September 2020 when the majority of people in the UK had neither been infected nor vaccinated against SARS-CoV-2. It included 52 people who lived with someone PCR-confirmed SARS-CoV-2 infection and who had therefore been exposed to the virus. Participants performed PCR tests at the start and 4 and 7 days later to determine if they developed an infection.

Blood samples from the 52 participants were collected within 1-6 days of exposure to the virus. This allowed the researchers to analyze the levels of pre-existing T cells induced by previous coronavirus infections of the common cold that also recognize SARS-CoV-2 virus proteins.

The researchers found that there were significantly higher levels of these cross-reactive T cells in the 26 people who weren't infected, compared with the 26 people who were infected. These T cells targeted the internal proteins within the SARS-CoV-2 virus, rather than the spike protein on the surface of the virus, to protect them from infection.

Current vaccines do not induce an immune response to these internal proteins. The researchers say that, coupled with our effective vaccines targeting existing spike proteins, these internal proteins offer a novel vaccine target that could provide long-lasting protection because T cell responses persist longer than antibody responses that decrease within a few months of vaccination.

Professor Ajit Lalvani, senior author of the study and director of the NIHR's Respiratory Infection Health Protection Research Unit at Imperial, says, “Our study provides the clearest evidence to date that T cells induced by Common cold coronaviruses play a protective role against SARS-CoV-2 infection. These T cells provide protection by attacking the proteins within the virus rather than the spike protein on its surface. "

“The spike protein is under intense immune pressure from the vaccine-induced antibody that drives the evolution of the vaccine's escape mutants. In contrast, the internal proteins targeted by the protective T cells we have identified mutate far less. Consequently, they are highly conserved among various SARS – CoV-2 variants, including omicron ”.

"Novel vaccines that include these internal conserved proteins would then induce broadly protective T cell responses that should protect against current and future variants of SARS-CoV-2."

The researchers note some limitations to their study, including the fact that because it is small and 88% of the participants were of white European ethnicity, it is not possible for them to model demographic factors.

The study was funded by the NIHR Health Protection Research Unit in Respiratory Infections and the Medical Research Council.