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A new study finds T cell immune response variation in recovered COVID-19 patients, including epitopes potentially important for vaccine design.

Coronavirus particle - blue 3D rendering

In the first in-depth analysis of SARS-CoV-2 specific T cell responses from recovered patients with varying degrees of COVID-19 disease severity, researchers have found greater memory T cell responses in the samples from patients with worse symptoms. The study, now published as a preprint on bioRxiv, was led by the MRC WIMM’s Professor Tao Dong, and included 42 patients from across the UK who had recovered from COVID-19.

So far, there have been few studies analysing SARS-CoV-2-specific T cell responses and their role in disease progression. Studying natural immunity to the virus, especially the role of SARS-CoV-2-specific T cells, is critical to fill the current knowledge gaps for improved vaccine design. While T cells are not thought to prevent the establishment of infection, there is good evidence in mice and humans that T cells provide partial protection against many acute viral infections, such as influenza, by promoting viral clearance and reducing the severity of symptoms.

The cases that Professor Dong and her collaborators studied included 28 mild and 14 severely ill patients and the researchers compared their T cell responses to those of 16 control donors. The team assessed the immune memory in the T cells within the samples and found that the breadth, magnitude and frequency of memory T cell responses provoked by COVID-19 were significantly higher in severe compared to mild COVID-19 cases. This effect was most marked in response to the SARS-CoV-2 spike, membrane, and ORF3a proteins.

Scientists suspect that deaths due to COVID-19 are related to both an overactive immune response and viral-induced lung disease, including pneumonia. It’s essential for us to uncover what is happening in patients’ immune systems for us to make informed decisions in the development of potential therapeutic interventions.

The researchers identified 39 separate peptides containing CD4+ and/or CD8+ T cell epitopes, which included six immunodominant epitope clusters (these are the type most easily recognised by the immune system and influence antibody specificity) targeted by T cells in many of the donors. In mild cases, more multi-cytokine producing CD8+ T cells were found than spike-specific CD8+ T cells. They also found a higher ratio of SARS-CoV-2-specific CD8+ to CD4+ T cell responses in the milder cases.

There are currently several ongoing vaccine trials but there are many uncertainties, including whether these vaccines could provide longstanding immunity. The majority of vaccines so far are aimed at inducing immunity to the SARS-CoV-2 spike protein, but we don’t yet know if this will be enough to induce full protective immunity to SARS-CoV-2. 

These immunodominant epitope clusters and peptides will provide critical tools to study the role of virus-specific T cells in further work to control the COVID-19 pandemic. The identification of T cell specificity and functionality associated with milder disease highlights the potential importance of including non-spike proteins within future vaccine design.

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