AI Summary
The article discusses how mRNA vaccines train T cells in waves against the spike protein of SARS-CoV-2. It highlights the importance of cellular immunity in providing protection against variants of concern by targeting conserved regions of the spike protein, potentially cross-reacting with other variants. Researchers conducted clonal-resolution analysis on T-cell responses to mRNA vaccination to understand the mechanism better. Longitudinal sequencing of TCR in 38 participants who received the Pfizer vaccine showed a kinetic profile of spike-reactive T-cell clones during repetitive vaccination. The findings were published in Cell Reports on March 7, 2024.
mRNA vaccines developed against the spike glycoprotein of severe acute respiratory syndrome type 2 coronavirus (SARS-CoV-2), displayed remarkable efficiency in combating coronavirus 19 (COVID-19). These vaccines work by triggering both cellular and humoral immune responses against the spike protein of the virus. Cellular immunity may play a more protective role than humoral immunity to variants of concerns (VOC) against SARS-CoV-2, as it targets the conserved regions of spike protein and possibly cross-reacts with other variants.
Since a single spike epitope is recognized by multiple T-cell clones, the mRNA vaccination-induced T-cell response may consist of multiple spike-reactive clones. Thus, it is important to understand the mechanism of mRNA vaccination-induced cellular immune response. However, to address this clonal-resolution analysis on T-cell responses to mRNA vaccination has not been performed yet.
To bridge this gap, a team of researchers, led by Associate Professor Satoshi Ueha, including Professor Kouji Matsushima from the Tokyo University of Science (TUS), Japan, Mr. Hiroyasu Aoki from the University of Tokyo, and Professor Toshihiro Ito from Nara Medical University, aimed to develop a kinetic profile of spike-reactive T-cell clones during repetitive mRNA vaccination. For this, they performed a longitudinal TCR sequencing on peripheral T cells of 38 participants who had received the Pfizer vaccine from before the vaccine to after the third vaccination and then analyzed the single-cell gene expression and epitope specificity of the clonotypes.
Their findings, published in Cell Reports on March 7, 2024, revealed that while the primary T-cell response of naïve T cells generally