Project description:Various RNAs have been shown to elicit innate immunity by activating endosomal PRRs such as Toll-like receptors 3/7/8 (TLR3/7/8), and cytosolic PRRs (e.g., retinoic acid-inducible gene I (RIG-I), melanoma differentiation-associated protein 5 (MDA5)). Such innate immunity provides cytokines and co-stimulation signals that are essential for adaptive immunomodulation.
Project description:Various RNAs have been shown to elicit innate immunity by activating endosomal PRRs such as Toll-like receptors 3/7/8 (TLR3/7/8), and cytosolic PRRs (e.g., retinoic acid-inducible gene I (RIG-I), melanoma differentiation-associated protein 5 (MDA5)). Such innate immunity provides cytokines and co-stimulation signals that are essential for adaptive immunomodulation.
Project description:The response to mRNA vaccines needs to be sufficient for immune cell activation and recruitment but moderate enough to ensure efficacious antigen expression. The choice of the cap structure and use of N1-methylpseudouridine (m1Ψ) instead of uridine, which have been shown to reduce RNA sensing by the cellular innate immune system, has led to improved efficacy of mRNA vaccine platforms. Understanding how RNA modifications influence the cell intrinsic immune response may help in the development of more effective mRNA vaccines. In the current study, we compared mRNA vaccines in mice against influenza virus using three different mRNA formats: uridine-containing mRNA (D1-uRNA), m1Ψ- modified mRNA (D1-modRNA), and m1Ψ-modified mRNA with a cap1 structure (cC1-modRNA). D1-uRNA vaccine induced a significantly different gene expression profile to the modified mRNA vaccines, with an upregulation of Stat1 and RnaseL, and increased systemic inflammation. This correlated with a significantly reduced antigen specific antibody responses and reduced protection against influenza virus infection compared to D1-modRNA and cC1-modRNA. Incorporation of m1Ψ alone without cap1 improved antibodies, but both modifications were required for the optimum response. Therefore, the incorporation of m1Ψ and cap1 alters protective immunity from mRNA vaccines by altering the innate immune response to the vaccine material
Project description:The mechanisms by which vaccines interact with human APCs remain elusive. We applied systems biology to define the transcriptional programs induced in human DCs by pathogens, innate receptor ligands and vaccines. Upon exposing DCs to influenza, Salmonella enterica and Staphylococcus aureus, we built a modular framework containing 204 pathogen-induced transcript clusters. Module fingerprints were then analyzed in DCs activated with 16 innate receptor ligands. This framework was then used to characterize human monocytes, IL-4 DC and blood DC subsets responses to 13 vaccines. Different vaccines induced distinct signatures based on pathogen type, adjuvant formulation and APC targeted. Fluzone broadly activated IL-4 DC whereas pneumovax only activated monocytes and gardasil (HPV) only activated CD1c+ mDC. This highlights that different antigen-presenting cells respond to different vaccines. Finally, the blood signatures from individuals vaccinated with fluzone or infected with influenza were interpreted using these modules. We identified a signature of adaptive immunity activation following vaccination and symptomatic infections, but not asymptomatic infections. These data, offered with a web interface, might guide the development of improved vaccines. 5 donors; 88 samples; duplicate technical replicates for the medium control for each donor for the BDCA1+ mDC population; single medium control for each donor for the BDCA3+ mDC population (15 total medium controls).
Project description:Arraystar Human circRNA Microarray is designed for the global profiling of human circRNAs. In this study, we applied a circRNA microarray to screen the potential biomarker for HCC. 20 samples extracted from plasma samples including HCC group before operation, and after operation, CH group and control group. Each group contained five samples.
Project description:We performed systems analyses of immune responses to the meningococcal polysaccharide (MPSV4) and conjugate (MCV4) vaccines in healthy adults. The goal was to identify innate gene signatures that correlate to antibody responses induced by these vaccines.