Summary Cross-reactive immune responses to SARS-CoV-2 have been observed in pre-pandemic cohorts and have been proposed to contribute to host protection. Here we evaluated 52 household COVID-19 contacts to capture immune responses at the earliest time points after exposure to SARS-CoV-2. Using a dual cytokine FLISpot assay in peripheral blood mononuclear cells, we enumerated the frequency of T cells specific for SARS-CoV-2 spike, nucleocapsid, membrane, envelope, and ORF1 epitopes that cross-react with endemic human coronaviruses. We observed higher frequencies of cross-reactive (p = 0.0139) and nucleocapsid-specific (p = 0.0355) IL-2-secreting memory T cells in contacts that remained PCR negative despite exposure (n = 26), compared to those who become PCR-positive (n = 26); no significant difference is observed in the frequency of responses to the spike protein, suggesting a limited protective role of spike cross-reactive T cells. Therefore, our results are consistent with cross-reactive memory T cells without pre-existing spikes protecting SARS-CoV-2-naïve contacts from infection, supporting the inclusion of non-spike antigens in vaccines. second generation. |
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A new study, published in Nature Communications and led by researchers at Imperial College London, 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 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 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 the National Heart and Lung Institute at Imperial, says: “Being exposed to the SARS-CoV-2 virus does not always result in infection, and we are keen 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 one form of protection, and I would like to emphasize that no one should rely on this alone. Instead, the best way to protect against COVID-19 is to get fully vaccinated, including vaccination with the booster dose."
The study began in September 2020 when most people in the UK had not been infected or 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. Participants took PCR tests at the beginning and 4 and 7 days later, to determine if they developed an infection.
Blood samples were taken from all 52 participants within 1 to 6 days of being exposed to the virus. This allowed the researchers to analyze the levels of pre-existing T cells induced by previous common cold coronavirus infections that also cross-recognize SARS-CoV-2 virus proteins [1].
The researchers found that there were significantly higher levels of these cross-reactive T cells in the 26 people who were not infected, compared to the 26 people who were infected. These T cells targeted the internal proteins of the SARS-CoV-2 virus, rather than the spike protein on the surface of the virus, to protect against infection.
Current vaccines do not induce an immune response to these internal proteins. Researchers say that, along with our existing vaccines targeting effective spike proteins, these internal proteins offer a new vaccine target that could provide long-lasting protection because T cell responses persist longer than antibody responses that wane. a few months after vaccination.
Professor Ajit Lalvani, lead 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 antibodies that drives the evolution of vaccine escape mutants. In contrast, the internal proteins targeted by the protective T cells we identified are highly mutated. less. Consequently, they are highly conserved between the different SARS-CoV-2 variants, including omicron. Therefore, new vaccines that include these conserved internal proteins would induce broadly protective T cell responses that should protect against the current variants and future of SARS-CoV-2".
The researchers point out some limitations to their study, including 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 on Respiratory Infections and the Medical Research Council.
