Single-Cell Transcriptome Profile During the Antibody Decline Phase Following Inactivated COVID-19 Vaccination

Zhongyi Zhu¹Yaling Huang²Jia-tong Sun³Meirong Li⁴Yong Chen⁴Fubaoqian Huang²Chuanyu Liu²Weijun Chen¹Jinmin Ma^1*

• ¹University of the Chinese Academy of Sciences, Beijing, China
• ²Shenzhen BGI Life Sciences Institute, Shenzhen, China
• ³Changchun University of Chinese Medicine, Changchun, China
• ⁴Huo-Yan Engineering Technology, ShenZhen, China

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, with antibody levels 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, indicating its role in antigen recognition and immune coordination. Cell-cell communication analysis further identified enhanced MHC-I signaling in high-titer groups, dominated by HLA-B interactions with CD8+ T cells, underscoring the importance of intercellular crosstalk in antibody maintenance. 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.