Investigating early immune responses across vaccine platforms through transcriptome analysis in human and murine models 3511

Abstract Description Vaccination is a critical tool in combating infectious diseases, supported by diverse platforms such as inactivated, viral vector, and mRNA vaccines. While mouse models are widely used for in vivo vaccine studies, significant differences exist between murine and human immune systems, particularly in early innate immune responses. To investigate innate immune responses on Day 2 post-vaccination, we analyzed RNA-seq data from human studies and murine samples (PBMCs and T/B cell-depleted lymph nodes), enabling a cross-species comparison of conserved and divergent pathways critical to vaccine efficacy. On Day 2, the viral vector vaccine showed the most significant changes in both human and mouse samples. RNA-seq analysis of lymph nodes enriched for innate immune cells in mice revealed that all vaccine platforms commonly activated pathways such as the MAPK pathway, TNFR-mediated NF-kB signaling, and TLR/NOD/cytosolic DNA signaling, indicating early activation of innate immune cells. Furthermore, Meta-analysis of DEGs revealed that inactivated vaccine responses largely overlap with those of viral vector vaccines, commonly activating pathways involved in immune regulation and cytokine signaling, while distinct pathway enrichment patterns were observed across vaccine platforms and between human and mouse samples. These findings provide valuable insights into the conserved and platform-specific innate immune mechanisms driving early vaccine responses across species. Funding Sources This research was supported by the National Research Foundation (NRF) funded by the Korean government (MSIT)(RS-2024-00398073). Topic Categories Vaccines and Immunotherapy (VAC)