Single-cell transcriptome profile during the antibody decline phase following inactivated COVID-19 vaccination

Introduction Variability in antibody responses among individuals following vaccination is a common phenomenon. This study employs single-cell transcriptome sequencing to characterize the transcriptomic features underlying these variations during the antibody decline phase after inactivated COVID-19 vaccination. Methods Sixty-five healthy volunteers received two doses of BBIBP-CorV. Antibody levels were measured 109–140 days post-vaccination. From these, 15 samples representing low, median, and high antibody titers were selected for PBMC single-cell RNA sequencing. Results Re-analysis of antibody kinetics revealed that titers during the decline phase are most strongly associated with long-term persistence. Differentially expressed genes were enriched in immune pathways including lymphocyte activation, antigen presentation (MHC-I and MHC-II), and interferon signaling. Significant variation in HLA genes, particularly HLA-B, was observed across PBMC cell types. Cell-cell communication analysis further identified enhanced MHC-I signaling in high-titer groups, dominated by HLA-B interactions with CD8+ T cells. Discussion These findings reveal a state of balanced immune alertness during the decline phase, providing insights into the cellular and molecular determinants of long-term humoral immunity and informing future vaccine design.