The emergence of a new pathogen, such as SARS-CoV-2 responsible for COVID-19, introduces novel challenges in vaccine development strategies and understanding the multifaceted effects of vaccines. Indeed, studies on SARS-CoV-2 mRNA vaccines, focusing on immune memory, protection from subsequent infections, and enhancement of booster vaccination outcomes, necessitate a comprehensive understanding of the immune system response. This entails integrating various approaches in cellular and molecular immunology, along with the utilization of advanced techniques.

The study by Sara Terzoli et al., "Expansion of memory Vδ2 T cells following SARS-CoV-2 vaccination revealed by temporal single-cell transcriptomics," examines the differentiation process and monitors the emergence of heterogeneity among unconventional gamma delta (γδ) T lymphocytes. By employing RNA/TCR-seq analysis at different time points of SARS-CoV-2 vaccine exposure history, this study represents the first comprehensive report on the immune response of γδ T cells following COVID-19 vaccination in the human population. Furthermore, through monitoring temporal transcriptomic changes at the single-cell level, it unveils the establishment of memory features by γδ T cells detected after repeated mRNA SARS-CoV-2 vaccination. Notably, the study illustrates that vaccination induces activation and expansion of γδ T cell clones, particularly within the specific subset of Vδ2 T cells, shaping their “effectorness” correlated with clonal expansion and development of memory profile.

In essence, SARS-CoV-2 vaccines (BNT162b2) "train" γδ T cells by triggering the memory process, which could potentially enhance immune recall in future challenges. Nevertheless, the long-term stability of memory γδ T cells linked to SARS-CoV-2 infection, both before and after vaccination, requires deeper examination. Importantly, this research presents a fresh perspective for investigating the concept of memory response in unconventional γδ T cells through time-related transcriptional RNA/TCR-seq analysis at the single-cell level.