AGE-ASSOCIATED ADAPTIVE IMMUNE TRANSCRIPTOMIC REMODELING FOLLOWING INACTIVATED SARS-COV-2 VACCINATION REVEALS DISTINCT CELLULAR AND FUNCTIONAL IMMUNE SIGNATURES
Abstract
The adaptive immune response to vaccination can be substantially influenced by aging, although the underlying transcriptional mechanisms across immune-cell populations remain incompletely understood. This study investigated age-associated adaptive immune transcriptomic remodeling following inactivated SARS-CoV-2 vaccination, with emphasis on CD4 T cells, CD8 T cells, and B cells. A retrospective transcriptomic analysis was performed using 36 RNAsequencing samples obtained from young and older individuals before and after vaccination. Following preprocessing and quality assessment, differential gene expression analysis was conducted separately for each immune-cell population. Protein-coding immune-related genes were subsequently identified and subjected to hierarchical clustering and Gene Ontology biological process enrichment analyses. Older individuals demonstrated broader transcriptomic perturbation across all immune-cell populations compared with younger individuals. CD4 T cells exhibited the greatest degree of differential expression, with 3,885 significant genes identified in older individuals. Immune-focused analysis further revealed extensive dysregulation of immune-associated genes, particularly in CD4 T cells and B cells. Functional
enrichment analysis identified pathways associated with B-cell proliferation, B-cell activation, immunoglobulin-mediated immune response, kinase-related signaling, inflammatory response, MAPK/ERK signaling, and dendritic-cell migration. Distinct clustering patterns additionally demonstrated clear transcriptomic segregation according to age group and vaccination status. These findings indicate that aging alters both the magnitude and functional direction of vaccineinduced adaptive immune responses at the transcriptomic level. The results support the value of immune-cell-specific transcriptomic profiling for understanding vaccination responses in aging populations and may contribute to future development of age-sensitive immunization strategies.
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