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Application of Next Generation Sequencing (RNA-seq and miRNA-seq) to study the molecular signature of Aluminium hydroxide adjuvant in ovine encephalon. [RNA-Seq]

ABSTRACT: We report the application of RNA sequencing technology for high-throughput profiling of the aluminium hydroxide adjuvant mechanism of action in an in vivo experiment on sheep treated with commercial vaccines, with the adjuvant alone or with PBS (control group). We mapped about 74.1 million sequence reads per sample to the sheep genome (build Oar3.1) and after filtering 16,369 genes were expressed, of which 14,387 were annotated genes in Ensembl and 1,982 were candidate lncRNAs. A total of 13, 63 and 76 differentialy expressed genes were identified in the Vaccine vs. Control, Adjuvant vs. Control and Adjuvant vs. Vaccine comparisons, respectively. Previously reported genes related to neuronal development, brain transport and neurotransmission, brain injury and neurodegenerative diseases associated with aluminum were found differentially expressed, namely VCAM1, TRPM4, GDF10 and NTN1.

ORGANISM(S): Ovis aries

PROVIDER: GSE128595 | GEO | 2020/10/02

REPOSITORIES: GEO

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Project description:Aluminum hydroxide, has long been employed as a vaccine adjuvant for its safety profile, although its precise mechanism of action remains elusive. In this study, we investigated the transcriptomic responses in sheep spleen following repetitive vaccination with aluminum adjuvanted vaccines and aluminum hydroxide alone. Notably, this work represents the first exploration of the sheep spleen transcriptome in such conditions. A total of 18 high-depth RNA-seq libraries were sequenced, resulting in a rich dataset which allowed isoform-level analysis also. The comparisons between vaccine-treated and control groups (V vs C) as well as between vaccine-treated and adjuvant-alone groups (V vs A) revealed significant alterations in gene expression profiles, including protein coding genes and long non-coding RNAs. Among the differentially expressed genes, many were associated with processes such as endoplasmic reticulum (ER) stress, immune response, cell cycle, and cellular senescence. The analysis of co-expression modules further indicated a correlation between vaccine treatment and genes related to ER stress and unfolded protein response. Surprisingly, adjuvant-alone treatment had little impact on the spleen transcriptome. Additionally, the role of alternative splicing in the immune response was explored. We identified isoform switches in genes associated with immune regulation and inflammation, potentially influencing protein function. In conclusion, this study provides valuable insights into the transcriptomic changes in sheep spleen following vaccination with aluminum adjuvanted vaccines and aluminum hydroxide alone. These findings shed light on the molecular mechanisms underlying vaccine-induced immune responses and emphasize the significance of antigenic components in aluminum adjuvant mechanism of action. Furthermore, the analysis of alternative splicing revealed an additional layer of complexity in the immune response to vaccination in a livestock species.

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Application of Next Generation Sequencing (RNA-seq and miRNA-seq) to study the molecular signature of Aluminium hydroxide adjuvant in ovine encephalon. [RNA-Seq]

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