Comparative single‐cell RNA sequencing analysis of immune response to inactivated vaccine and natural SARS‐CoV‐2 infection

Abstract

Uncovering the immune response to an inactivated SARS‐CoV‐2 vaccine (In‐Vac) and natural infection is crucial for comprehending COVID‐19 immunology. Here we conducted an integrated analysis of single‐cell RNA sequencing (scRNA‐seq) data from serial peripheral blood mononuclear cell (PBMC) samples derived from 12 individuals receiving In‐Vac compared with those from COVID‐19 patients. Our study reveals that In‐Vac induces subtle immunological changes in PBMC, including cell proportions and transcriptomes, compared with profound changes for natural infection. In‐Vac modestly upregulates IFN‐α but downregulates NF‐κB pathways, while natural infection triggers hyperactive IFN‐α and NF‐κB pathways. Both In‐Vac and natural infection alter T/B cell receptor repertoires, but COVID‐19 has more significant change in preferential VJ gene, indicating a vigorous immune response. Our study reveals distinct patterns of cellular communications, including a selective activation of IL‐15RA/IL‐15 receptor pathway after In‐Vac boost, suggesting its potential role in enhancing In‐Vac‐induced immunity. Collectively, our study illuminates multifaceted immune responses to In‐Vac and natural infection, providing insights for optimizing SARS‐CoV‐2 vaccine efficacy.