Transcriptomic propensity of TNFhigh MAIT cells to provide B cell help following SARS-CoV-2 vaccination

Recent findings indicated an association between MAIT cells and the immune response to the BNT162b2 vaccine, where MAIT cell frequency was associated with an increased adaptive immune response. Herein, to investigate the effect of repeated SARS-CoV-2 vaccinations on MAIT cells, we performed a longitudinal 5’ scRNA-seq coupled with scTCR-seq analysis on the peripheral blood samples of six healthy adults naïve for the SARS-CoV-2 infection and immunized with the two doses of the mRNA-based vaccine BNT162b2. Taking advantages of computational approaches, including functional pathway enrichment analyses and the gene expression–effector cell-polarization’s fate probabilities correlation (RNA Velocity and CellRank), we identified MAIT cells as the major source of TNF-α across circulating lymphocytes, and this TNFhigh signature increased upon the second administration of the vaccine. Notably, the increased TNF-α expression correlated with SARS-CoV-2 specific antibody titers. Therefore, by modeling the intercellular communication with the NicheNet algorithm, we observed that the TNF-α-profile predicts the transcriptional changes of conventional switched memory B cells, deputed to high-affinity long-term memory. Overall, our results indicate that MAIT cells promote B cell functionality in response to the vaccine, favoring effective and long-term protection against SARS-CoV-2 infection, suggesting the use of MAIT cells as cellular adjuvants in mRNA-based vaccines.