Upregulated CD8+ MAIT cell differentiation and KLRD1 gene expression after inactivated SARS-CoV-2 vaccination identified by single-cell sequencing

Abstract

Background: The primary strategy for reducing the incidence of COVID-19 is SARS-CoV-2 vaccination. Few studies have explored T cell subset differentiation and gene expressions induced by SARS-CoV-2 vaccines. Our study aimed to analyze T cell dynamics and transcriptome gene expression after inoculation with an inactivated SARS-CoV-2 vaccine by using single-cell sequencing.

Methods: Single-cell sequencing was performed after peripheral blood mononuclear cells were extracted from three participants at four time points during the inactivated SARS-CoV-2 vaccination process. After library preparation, raw read data analysis, quality control, dimension reduction and clustering, single-cell T cell receptor (TCR) sequencing, TCR V(D)J sequencing, cell differentiation trajectory inference, differentially expressed genes, and pathway enrichment were analyzed to explore the characteristics and mechanisms of postvaccination immunodynamics.

Results: Inactivated SARS-CoV-2 vaccination promoted T cell proliferation, TCR clone amplification, and TCR diversity. The proliferation and differentiation of CD8⁺ mucosal-associated invariant T (MAIT) cells were significantly upregulated, as were KLRD1 gene expression and the two pathways of nuclear-transcribed mRNA catabolic process, nonsense-mediated decay, and translational initiation.

Conclusion: Upregulation of CD8⁺ MAIT cell differentiation and KLRD1 expression after inactivated SARS-CoV-2 vaccination was demonstrated by single-cell sequencing. We conclude that the inactivated SARS-CoV-2 vaccine elicits adaptive T cell immunity to enhance early immunity and rapid response to the targeted virus.

Keywords: CD8+ MAIT cell differentiation; COVID-19; KLRD1 gene; inactivated SARS-CoV-2 vaccine; single-cell sequencing.