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MOG-encoding DNA vaccines ameliorate EAE and display neuroprotective effects in treated mice summary

ABSTRACT: Vaccination with naked DNA encoding myelin basic protein represents a promising therapeutic strategy in multiple sclerosis (MS). In this study, we assessed the potential of vaccination with a DNA construct coding for the myelin oligodendrocyte glycoprotein (MOG), an important candidate autoantigen in MS, to induce tolerance and protect against experimental autoimmune encephalomyelitis (EAE). Herein, we demonstrated that MOG-DNA vaccination reduced the clinical and histopathological signs of EAE when administered in both prophylactic and therapeutic settings. Further mechanistic experiments revealed that the protective effects of MOG-DNA vaccines were associated with a reduction of antigen-specific Th1 and Th17 cellular immune responses and expansion of regulatory T cells in periphery, and up-regulation in the central nervous system of genes encoding neurotrophic factors and proteins involved in remyelination. These results may set the rationale for the use of MOG-based DNA vaccines to induce tolerance in MS patients.

ORGANISM(S): Mus musculus

PROVIDER: GSE30482 | GEO | 2011/07/08

SECONDARY ACCESSION(S): PRJNA143471

REPOSITORIES: GEO

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MOG-encoding DNA vaccines ameliorate EAE and display neuroprotective effects in treated mice summary

Project description:Vaccination with naked DNA encoding myelin basic protein represents a promising therapeutic strategy in multiple sclerosis (MS). In this study, we assessed the potential of vaccination with a DNA construct coding for the myelin oligodendrocyte glycoprotein (MOG), an important candidate autoantigen in MS, to induce tolerance and protect against experimental autoimmune encephalomyelitis (EAE). Herein, we demonstrated that MOG-DNA vaccination reduced the clinical and histopathological signs of EAE when administered in both prophylactic and therapeutic settings. Further mechanistic experiments revealed that the protective effects of MOG-DNA vaccines were associated with a reduction of antigen-specific Th1 and Th17 cellular immune responses and expansion of regulatory T cells in periphery, and up-regulation in the central nervous system of genes encoding neurotrophic factors and proteins involved in remyelination. These results may set the rationale for the use of MOG-based DNA vaccines to induce tolerance in MS patients. We analyzed brain and spinal cord samples from five treated and five control mice

2011-07-08 | E-GEOD-30482 | biostudies-arrayexpress

Comparative genomic hybridization of experimental autoimmune encephalomyelitis (EAE)-susceptible DA and EAE-resistant PVG rat strains stimulated with myelin oligodendrocyte glycoprotein (MOG) to identify the alternative splicing.

Project description:Experimental autoimmune encephalomyelitis (EAE)-susceptible DA and EAE-resistant PVG rats were immunized with myelin oligodendrocyte glycoprotein (MOG) to induce an autoimmune response. Seven days later draining inguinal lymph nodes were removed. 2 conditions were examined: 'ex vivo' and 'MOG restimulated', which involved 24hrs of incubation with an encephalogenic MOG 91-108 peptide.

2009-11-01 | E-MEXP-2237 | biostudies-arrayexpress

RNA seq on SP specific CD8+ T cells, Ly49+ and Ly49-CD8+ T cells from MOG and MOG + SP immunized mice [RNA-Seq]

Project description:In experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis (MS), induction generates successive waves of clonally expanded CD4+, CD8+, and gd+ T cells in the blood and central nervous system, similar to gluten challenge studies of Celiac patients. In MS patients, we also observe major expansions of CD8+ T cells. In EAE, we find that most expanded CD4+ T cells are specific for the inducing myelin peptide MOG35-55 but in contrast, peptide ligands derived from a yeast peptide-MHC display library for some of the clonally expanded CD8+ T cells inhibit disease by suppressing the proliferation of MOG-specific CD4+ T cells. These results suggest the induction of autoreactive CD4+ T cells triggers an opposing mobilization of regulatory CD8+ T cells.

2019-08-08 | GSE130975 | GEO

Gene expression profiling of mouse experimental autoimmune encephalomyelitis (EAE) from spinal cord preparations of opticospinal EAE (OSE) and MOG-induced EAE

Project description:Genetic opticospinal EAE (OSE) and MOG-induced EAE (MOG-EAE) are two experimental autoimmune encephalomyelitis (EAE) mouse models of human multiple sclerosis. For the OSE model, double-transgenic 2D2 (TCRMOG) x IgHMOG mice were used. For MOG-EAE, wildtype C57BL/6 mice were immunized with a MOG peptide consisting of the amino acids 35-55, administered in complete Freund’s adjuvant containing 5mg / ml Mycobacterium tuberculosi. The severity of EAE was rated on the scale 0: healthy animal; 1: animal with a flaccid tail; [...]; 4: animal with both hind legs paralyzed. The case groups in the experiment were: OSE1: OSE with disease score 1; OSE4: OSE with disease score 4; MOG4: MOG-EAE injected with both MOG and adjuvant, with disease score 4. The control groups in the experiment were: OSE0: OSE with disease score 0; CFA: C57BL/6 mice injected only with adjuvant (no MOG); WT: Wildtype C57BL/6 mice. The aim of the experiment was to assess gene expression differences 1) between OSE4 and OSE0, 2) between OSE1 and OSE0, and 3) between MOG4 and CFA. For control, WT was compared to OSE0 and CFA. Subsequently, differentially expressed transcripts were compared, first, between the OSE4 vs. OSE0 and the MOG4 vs. CFA contrasts (different EAE models) and, second, between the OSE4 vs. OSE0 and the OSE1 vs. OSE0 contrasts (different EAE severity).

2020-08-21 | E-MTAB-9132 | biostudies-arrayexpress

Transcription profiling by tiling array of Rattus norvegicus lymph nodes from experimental autoimmune encephalomyelitis susceptible DA and congenic R23 animal strains stimulated with myelin oligodendrocyte glycoprotein.

Project description:Experimental autoimmune encephalomyelitis (EAE)-susceptible DA and EAE-resistant congenic R23 rats were immunized with myelin oligodendrocyte glycoprotein (MOG) to induce an autoimmune response. Seven days later draining inguinal lymph nodes were removed. 2 conditions were examined: 'ex vivo' and 'MOG restimulated', which involved 24hrs of incubation with an encephalogenic MOG 91-108 peptide.

2010-12-31 | E-MEXP-2703 | biostudies-arrayexpress

F2833 scRNA-seq data for manuscript "Therapeutic vaccine containing a novel liposomal adjuvant shifts pathogenic Th17 cells into a Tr1-like phenotype"

Project description:Th17 cells can transdifferentiate into other T cell subsets in the context of infections or inflammatory conditions. In many autoimmune diseases, autoantigen-specific Th17 cells play a pivotal role in disease pathogenesis, however, there have been no attempts to target Th17 cell plasticity using vaccines. We aimed to change the phenotype of existing Th17 cells by a protein-in-adjuvant approach and found that antigen formulated in all-trans retinoic acid (ATRA)-containing cationic liposomes (CAF16) effectively inhibited existing Th17 responses. Strikingly, transcriptomic analysis of sorted Th17 cells from IL-17 fate reporter mice revealed a shift of antigen-specific Th17 cells to exTh17 cells, expressing functional markers associated with T cell regulation and tolerance. In addition, vaccination with myelin-specific (MOG) antigen in CAF16 reduced Th17 responses and alleviated disease in the experimental autoimmune encephalomyelitis (EAE) mouse model of MS. This highlights CAF16 as a novel delivery system for ATRA with potential for changing the phenotype of existing Th17 cells in the context of immune mediated diseases.

2024-02-27 | GSE240801 | GEO

F2702 bulk RNA-seq data for manuscript "Therapeutic vaccine containing a novel liposomal adjuvant shifts pathogenic Th17 cells into a Tr1-like phenotype"

2024-02-27 | GSE240800 | GEO

Mus musculus

Project description:MOG-encoding DNA vaccines ameliorate EAE and display neuroprotective effects in treated mice summary

| PRJNA143471 | ENA

Treatment with nanoliposomes loaded with ITE and MOG(35-55) ameliorates EAE

Project description:To evaluate the therapeutic potential of NLP(ITE+MOG) in a mouse model of secondary progressive multiple sclerosis, we induced EAE in NOD mice and initiated weekly treatment with nanoliposomes beginning at 35 days post immunization during the chronic phase of disease. NLP(ITE+MOG) administration ameliorated EAE, and the transcriptional analysis of CNS-resident astrocytes, microglia and monocytes revealed decreased expression of genes associated with pro-inflammatory responses and neurodegeneration.

2021-08-04 | GSE155711 | GEO

Transcriptome profiling of a backcross between experimental autoimmune encephalomyelitis (EAE)-susceptible DA and EAE-resistant PVG rat strains to identify expression quantitative trait loci.

Project description:The aim of the experiment is to characterize the genetics and mechanisms of the inflammatory response after induction of experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis, by studying the genome wide expression in the spleen in late disease. A backcross was created between EAE-susceptible DA and EAE-resistant PVG rats. At day 35 after induction of EAE with myelin oligodendrocyte glycoprotein (MOG) in these rats, spleens were taken for transcriptional profiling.

2013-08-10 | E-MTAB-784 | biostudies-arrayexpress

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