T Cells From Common Colds Cross-Protect Against Infection With SARS-CoV-2

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

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

Dr Rhia Kundu, first author of the study, from Imperial’s National Heart & Lung Institute, says: “Being exposed to the SARS-CoV-2 virus doesn’t always result in infection, and we’ve been keen to understand why. We found that high levels of pre-existing T cells, created by the body when infected with other human coronaviruses like the common cold, can protect against COVID-19 infection.

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

The study began in September 2020 when most people in the UK had neither been infected nor vaccinated against SARS-CoV-2. It included 52 people who lived with someone with PCR-confirmed SARS-CoV-2 infection and who had therefore been exposed to the virus. The participants did PCR tests at the outset and 4 and 7 days later, to determine if they developed an infection.

Blood samples from the 52 participants were taken within 1-6 days of them being exposed to the virus. This enabled the researchers to analyse the levels of pre-existing T cells induced by previous common cold coronavirus infections that also cross-recognise proteins of the SARS-CoV-2 virus [1].

The researchers found that there were significantly higher levels of these cross-reactive T cells in the 26 people who did not become infected, compared to the 26 people who did become infected. These T cells targeted internal proteins within the SARS-CoV-2 virus, rather than the spike protein on the surface of the virus, to protect against infection [2].

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

Professor Ajit Lalvani, senior author of the study and Director of the NIHR Respiratory Infections 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 proteins within the virus, rather than the spike protein on its surface.

“The spike protein is under intense immune pressure from vaccine-induced antibody which drives evolution of vaccine escape mutants. In contrast, the internal proteins targeted by the protective T cells we identified mutate much less. Consequently, they are highly conserved between the various SARS-CoV-2 variants, including omicron. New vaccines that include these conserved, internal proteins would therefore induce broadly protective T cell responses that should protect against current and future SARS-CoV-2 variants.”

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

[1] These included external surface proteins (spike, membrane and envelope proteins) on the surface of the SARS-CoV-2 virus, and internal proteins, including nucleocapsid (which packages the virus’ genetic material) and ORF1 (a part of SARS-CoV-2’s replicative machinery).

[2] The targeted internal proteins of SARS-CoV-2 included nucleocapsid and ORF1 only.