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

Unlike mRNA vaccines based only on the spike protein, inactivated severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccines should induce a diversified T cell response recognizing distinct struc-tural 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 with 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 infec-tion.

Automated summary

This study compares the T cell responses in individuals vaccinated with inactivated SARS-CoV-2 or mRNA vaccines. Compared to mRNA vaccines, inactivated vaccines induce a lower magnitude of spike-specific T cell response, but the combination of other protein-specific T cell responses is quantitatively comparable to the spike-specific T cell response induced by mRNA vaccines and can efficiently tolerate the mutations of the Omicron lineage. However, this multi-protein-specific T cell response is primarily mediated by selective priming of CD4 T cells rather than coordinated expansion of CD4 and CD8 T cells.