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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. [miRNA-Seq]

ABSTRACT: We report the application of miRNA sequencing technology for high-throughput profiling of the aluminium hydroxide adjuvant mechanism of action in an in vivo experiment on sheep. We mapped about 13.1 million sequence reads per sample to the sheep genome (build Oar3.1) and identified 299 miRNAs in the encephalon of sheep treated with commercial vaccines, with the adjuvant alone or with PBS (control group). A total of 2, 38 and 7 differentialy expressed miRNAs were identified in the Vaccine vs. Control, Adjuvant vs. Control and Adjuvant vs. Vaccine comparisons, respectively. Furthermore, miRNA target prediction was performed and it was integrated with previous RNA-seq data in the same animals to predict reliable miRNA-mRNA interactions. Previously reported miRNAs related to brain injury and neurodegenerative diseases were found differentially expressed. Within the negatively correlated targets of the differentially expressed miRNAs there are factors that are clearly related with mitochondria, to maintenance of neuronal polarity and axon growth and to apoptosis. Taken together, our analysis provides characterization of alterations in the miRNAome caused by the aluminium adjuvant alone, while the commercial vaccine not cause great changes, and identifies some targets of the differentially expressed miRNAs which have been previously linked to mitochondrial dysfunction. Aluminum might be causing an imbalance in metal ion levels, among them Mg, in the parietal lobe cortex of animals vaccinated with the adjuvant alone.

ORGANISM(S): Ovis aries

PROVIDER: GSE128596 | 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. [miRNA-Seq]

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