Majority of T-cell targets not on COVID-19 Spike protein, study finds

New research has identified the precise immunodominant targets of T cells isolated from COVID-19 convalescent patients, which the scientists say could be used in vaccine development. They found that most are not located on the Spike (S) protein of the virus, the target of most vaccines currently in development. 

According to TScan Therapeutics, which conducted the research, the targets were shared among patients with the same human leukocyte antigen (HLA) type and were primarily located outside the S protein. The company has submitted these findings for scientific review and publication with the goal of guiding COVID-19 vaccine development that may confer broad, durable immunity by eliciting a robust T-cell response. These discoveries may also enable the development of reliable T-cell-based diagnostic tests to determine longer-term immunity and inform the development of therapeutic agents.

The researchers mapped the memory CD8+ T-cell responses of 43 convalescent COVID-19 patients, with a focus on the six most prevalent HLA types. For each HLA type, patient T cells largely recognised the same three to eight immunodominant epitopes. Importantly, a majority of the identified T-cell targets were not found in the S protein of the virus. 

Additionally, these immunodominant targets were not found in other coronaviruses, limiting the likelihood that prior coronavirus infections may confer immunity to COVID-19.

“COVID-19 vaccine development efforts have been progressing rapidly, but to date remain largely focused on eliciting a neutralising antibody response against the virus’ S protein,” said Dr Gavin MacBeath, Chief Scientific Officer at TScan. “Because antibodies to SARS-CoV-2 appear to diminish over time, there is growing concern that if vaccines do not also generate a strong T-cell response, they may only provide short-term immunity. An increasing body of evidence suggests that the T-cell response is important in the defence against COVID-19 and T cells that recognise coronaviruses tend to persist much longer than antibodies. In this study, we identified a short list of the most critical T-cell targets that could form the basis of a second-generation vaccine, potentially an important follow-on approach to the S protein vaccines that are currently being developed.”

The research was pre-published in medRxiv.