A comparative characterization of SARS-CoV-2-specific T cells induced by mRNA or inactive virus COVID-19 vaccines

Abstract

Unlike mRNA vaccines based only on the Spike protein, inactivated SARS-CoV-2 vaccines should induce a diversified T cell response recognizing distinct structural proteins. Here we perform a comparative analysis of SARS-CoV-2 specific T cells in healthy individuals following vaccination with inactivated SARS-CoV-2 or mRNA vaccines. Relative to Spike mRNA vaccination, inactivated vaccines elicit a lower magnitude of Spike-specific T cells, but the combination of Membrane, Nucleoprotein and Spike-specific T cell response is quantitatively comparable to the sole Spike T cell response induced by mRNA vaccine, and they efficiently tolerate the mutations characterizing the Omicron lineage. However, this multi-protein specific T cell response is not mediated by a coordinated CD4 and CD8 T cell expansion but by selective priming of CD4 T cells. These findings can help in understanding the role of CD4 and CD8 T cells in the efficacy of the different vaccines to control severe COVID-19 after Omicron infection.