Clonal-Resolution Analysis of T Cell Responses to mRNA Vaccination Conducted

mRNA vaccines targeting the spike glycoprotein of SARS-CoV-2 have shown remarkable efficacy in combating COVID-19 by eliciting both cellular and humoral immune responses. Recent research suggests that cellular immunity, targeting conserved regions of the spike protein, may offer more protection against variants of concern. However, a detailed clonal-resolution analysis of T-cell responses to mRNA vaccination hadn't previously been conducted.

To bridge this gap, a team of researchers led by Associate Professor Satoshi Ueha from Tokyo University of Science embarked on a study to track the kinetics of spike-reactive T cell clones following repetitive mRNA vaccination. Their findings, published in Cell Reports, revealed distinct patterns of T-cell responses. "Early responders" containing memory T cells against common coronaviruses expanded after the first shot, while "main responders" emerged after the second shot and "third responders" after the third shot.

The study highlighted a shift in clonal dominance among T-cell populations post-vaccination, with effector-memory T cells predominating after successive doses. Notably, the third vaccination led to the selection of better-responding clones, supporting the concept of immunodominance shift and intra-epitope shifts within spike epitopes. 

“Our analysis suggests that T cells can ‘re-write’ themselves and reshape their memory populations after successive vaccinations. This re-writability not only maintains the number of memory T cells but also maintains diversity that can respond to different variants of pathogens. Moreover, by tuning the replacement of memory cells, more effective vaccines can be developed that can also be tailored to an individual’s unique immune response,” Prof. Ueha added.