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Transcriptome atlas of injection site response reveals initial mechanisms of mRNA vaccine immunity

ABSTRACT: Transcriptome atlas of injection site response reveals initial mechanisms of mRNA vaccine immunity

PROVIDER: PRJNA999716 | ENA |

REPOSITORIES: ENA

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Transcriptome atlas of injection site response reveals initial mechanisms of mRNA vaccine immunity

Project description:Precise immunological mechanisms of mRNA vaccines have still not been fully elucidated, especially the initial immune responses at the injection site. Here, by constructing a single-cell atlas of injection site responses of mRNA vaccine, we show that stromal inflammatory responses and type I interferon responses dominate initial transcriptional reactions elicited by mRNA vaccines at the injection site. Tracking down the fates of the delivered mRNA revealed that injection site fibroblasts are highly enriched with the delivered mRNA, and they express IFN-β specifically in response to the mRNA component, not to the LNP. Accordingly, migratory dendritic cells highly expressing interferon stimulated genes (mDC_ISG) were found specifically in muscle and draining lymph nodes of mRNA vaccine injected mice, compared to the empty LNP injected mice. Co-administration of IFN-β and LNP robustly induced mDC_ISGs at the injection site and substantially enhanced antigen-specific CD8 T cell responses. Collectively, these data elucidate earliest mechanisms of the mRNA vaccine and highlight the underappreciated immunogenic role of the mRNA component in the mRNA vaccine.

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Project description:The skin plays a crucial role in host defences against microbial attack and the innate cells must provide the immune system with sufficient information to organize these defences. This unique feature makes the skin a promising site for vaccine administration. Although cellular innate immune events during vaccination have been widely studied, initial events remain poorly understood. Our aim is to determine molecular biomarkers of skin innate reaction after intradermal (i.d.) immunization. Using an ex vivo human explant model from healthy donors, we investigated by NanoLC-MS/MS analysis and MALDI-MSI imaging, to detect innate molecular events (lipids, metabolites, proteins) few hours after i.d. administration of seasonal trivalent influenza vaccine (TIV). This multimodel approach allowed to identify early molecules differentially expressed in dermal and epidermal layers at 4 and 18 h after TIV immunization compared with control PBS. In the dermis, the most relevant network of proteins upregulated were related to cell-to-cell signaling and cell trafficking. The molecular signatures detected were associated with chemokines such as CXCL8, a chemoattractant of neutrophils. In the epidermis, the most relevant networks were associated with activation of antigen-presenting cells and related to CXCL10. Our study proposes a novel step-forward approach to identify biomarkers of skin innate reaction.

2020-01-29 | PXD017313 | Pride

Cell atlas of mouse colon tissue from the initial stage of colitis

Project description:Inflammation dramatically alters the gut microenvironment. To investigate the composition and transcriptome changes of various intestinal cell populations during the initial phase of inflammation, and the underlying cellular interactions, we delineated a single-cell atlas of the mouse colon treated with DSS on the day 2 of colitis.

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Transcription profiling of liver from flounder after injection with a vaccine containing killed Aeromonas salmonicida, the bacterium responsible for furunculosis

Project description:To study the effects of bacterial infection upon gene expression changes in flounder liver fish were artificially "infected" by injection with a commercial water-based vaccine containing killed Aeromonas salmonicida, the bacterium responsible for furunculosis, which, as its name describes, presents as external lesions (furuncles, "lumps"). This disease occurs in flounder as well as in salmonids. Flounders were treated by intraperitoneal injection with 1ml/kg Furunculosis vaccine (Schering-Plough, Aquavac Furovac 5, batch number FNM/C/007). 30 control fish were injected with 1% saline. Animals were then maintained unfed in static aerated sea water tanks in a constant temperature containment aquarium. Water was renewed every 2 days. After 1, 2, 4, 8, and 16 days, 6 vaccine treated and 6 saline control fish were removed, killed by a blow to the head and samples of liver tissue were immediately homogenized in TriReagent prior to gene expression profiling. Microarray experiments consisted an individual array for each of 4 or 5 fish from each timepoint and each treatment compared with an artificial reference sample.

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Project description:Cell atlas of mouse colon tissue from the initial stage of colitis

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