Modulating IL-1β and its receptors shapes spike-specific CD4 +T cell responses to mRNA vaccination

Abstract

Abstract Augmenting and sustaining a durable immunity provided by COVID-19 mRNA vaccines is important. Thus, we characterized S protein-specific CD4 +T cells in healthy individuals who received COVID-19 mRNA vaccines utilizing single cell RNA-seq and mass cytometry. In humans, S protein-specific CD4 +T cells highly expressed IL-1 receptor (R) 1 and its decoy receptor IL-1R2. IL-1b promoted IFN-g expression by S protein-stimulated CD4 +T cells, which was furthered by adding anti-IL-1R2-blocking antibodies, supporting the functional implications of IL-1R1 and IL-1R2. Following the 2 nddose of vaccination, IL-1R1 expression increased while IL-1R2 expression decreased in S protein-specific CD4 +T cells. The expression levels of such cytokine receptors correlated with S-specific antibody production. Our findings provide novel insight into the role of IL-1β and its receptor system in developing COVID-19 mRNA vaccine-induced CD4 +T cell immunity. Supported by grants from NIH (1R01AG056728 and R01AG055362) and Quest Diagnostics.