Revealing dynamic transcriptomic and immune cell signatures underlying heterogeneous responses to influenza vaccination

Abstract

Background

Seasonal influenza can cause variable respiratory infections and severe complications, and vaccination remains essential for infection control. Nevertheless, substantial inter-individual variability in vaccine immune responses persists, and the molecular determinants remain poorly defined. This study aimed to elucidate the temporal gene expression patterns and immune cell dynamics associated with vaccine response through longitudinal transcriptomic and immune cell data.

Methods

We utilized gene expression, immune cell composition, and immune response data from Immune Signatures Data Resource (IS2). Differential expression and time-series analyses identified key transcriptional features and dynamic patterns linked to vaccine response. Weighted gene co-expression network analysis (WGCNA) revealed gene modules associated with vaccine response and elucidating their pathway enrichment characteristics. Finally, the linear mixed-effects model was used to examine the temporal trends of 12 immune cell subsets across response groups, while generalized linear mixed models (GLMM) were employed to assess associations between differential expression genes and immune cell.

Results

Overall analysis revealed the most differential expression genes at day 1 post-vaccination and time-series analysis identified 15 genes with significant dynamic changes. Notably, interferon-stimulated genes GBP1 and GBP2 exhibited transient upregulation in high responders, showing significant positive correlation with antibody titer increases. WGCNA analysis identified 3 immune response-associated modules that were primarily enriched in immune regulation and cell signaling pathways. Immune cell analysis revealed a distinct biphasic pattern of Naive B cells in the high responders. Furthermore, JAG2 was found to be associated with multiple immune cell populations. These findings reveal a complex regulatory network underlying influenza vaccine response.

Conclusion

Our study highlights the importance of early gene expression and dynamic immune cell changes following influenza vaccination in shaping the immune response. The identification of transiently regulated genes alongside specific immune cell dynamics suggests they may serve as key determinants of vaccine response.