The main work of this study can be summarized as follows: (I) we systematically analysed the transcriptome profiles of 29 medical staff members receiving an inactivated vaccine compared with three healthy controls and three COVID-19-infected patients; (II) we identified several genes, including MAPK1, CDC42, PPP2CA, EP300, YWHAZ and NRAS that were robustly correlated with the vaccine; (III) NRAS, YWHAB, SMARCA5, PPP1CC and CDC5L were identified as shared response genes, which were significantly downregulated in vaccinated individuals compared with infected patients. Here, EP300 is linked to COVID-19.