Publication date: Sep 29, 2025
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. 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. 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. 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.

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Semantics
| Type | Source | Name |
|---|---|---|
| disease | MESH | COVID-19 |
| pathway | REACTOME | Interferon Signaling |
| pathway | REACTOME | Cell-Cell communication |
| disease | MESH | Infection |
| pathway | REACTOME | Reproduction |
| disease | MESH | Mul |
| drug | DRUGBANK | Guanosine |
| disease | MESH | included |
| drug | DRUGBANK | Cycloserine |
| disease | MESH | DCs |
| pathway | REACTOME | Immune System |
| disease | MESH | inflammation |
| pathway | REACTOME | Innate Immune System |
| pathway | REACTOME | Adaptive Immune System |
| drug | DRUGBANK | Edetic Acid |
| drug | DRUGBANK | Phosphate ion |
| disease | MESH | PBS |
| drug | DRUGBANK | Flunarizine |
| disease | MESH | FBS |
| drug | DRUGBANK | Dimethyl sulfoxide |
| drug | DRUGBANK | Nitrogen |
| drug | DRUGBANK | Water |
| drug | DRUGBANK | Human Serum Albumin |
| drug | DRUGBANK | Coenzyme M |
| disease | MESH | STAR |
| drug | DRUGBANK | Pidolic Acid |
| disease | MESH | PCA |
| disease | MESH | pct |
| disease | MESH | Ad5 |
| disease | MESH | rheumatic disease |
| disease | MESH | RMD |
| disease | MESH | tumor |
| disease | MESH | Park |
| disease | MESH | Dis |
| pathway | REACTOME | Translation |
| drug | DRUGBANK | Carboxyamidotriazole |
| disease | MESH | influenza |