Intradermal vaccination prevents anti-MOG autoimmune encephalomyelitis in macaquesResearch in context
Background: Autoimmune demyelinating diseases (ADD) are a major cause of neurological disability due to autoreactive cellular and humoral immune responses against brain antigens. A cure for chronic ADD could be obtained by appropriate immunomodulation. Methods: We implemented a preclinical scheme to...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2019-09-01
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| Series: | EBioMedicine |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396419305742 |
| _version_ | 1818856414011981824 |
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| author | Claire-Maëlle Fovet Lev Stimmer Vanessa Contreras Philippe Horellou Audrey Hubert Nabila Seddiki Catherine Chapon Sabine Tricot Carole Leroy Julien Flament Julie Massonneau Nicolas Tchitchek Bert A. 't Hart Sandra Zurawski Peter Klucar Philippe Hantraye Kumaran Deiva Gerard Zurawski SangKon Oh Roger Le Grand Ché Serguera |
| author_facet | Claire-Maëlle Fovet Lev Stimmer Vanessa Contreras Philippe Horellou Audrey Hubert Nabila Seddiki Catherine Chapon Sabine Tricot Carole Leroy Julien Flament Julie Massonneau Nicolas Tchitchek Bert A. 't Hart Sandra Zurawski Peter Klucar Philippe Hantraye Kumaran Deiva Gerard Zurawski SangKon Oh Roger Le Grand Ché Serguera |
| author_sort | Claire-Maëlle Fovet |
| collection | DOAJ |
| description | Background: Autoimmune demyelinating diseases (ADD) are a major cause of neurological disability due to autoreactive cellular and humoral immune responses against brain antigens. A cure for chronic ADD could be obtained by appropriate immunomodulation. Methods: We implemented a preclinical scheme to foster immune tolerance to myelin oligodendrocyte glycoprotein (MOG), in a cynomolgus-macaque model of experimental autoimmune encephalomyelitis (EAE), in which administration of recombinant human MOG (rhMOG) elicits brain inflammation mediated by MOG-autoreactive CD4+ lymphocytes and anti-MOG IgG. For immunotherapy, we used a recombinant antibody (Ab) directed against the dendritic cell-asialoglycoprotein receptor (DC-ASGPR) fused either to MOG or a control antigen PSA (prostate-specific antigen). Findings: rhMOG and the anti-DC-ASGPR-MOG were respectively detected in CD1a+ DCs or CD163+ cells in the skin of macaques. Intradermal administration of anti-DC-ASGPR-MOG, but not control anti-DC-ASGPR-PSA, was protective against EAE. The treatment prevented the CD4+ T cell activation and proinflammatory cytokine production observed in controls. Moreover, the administration of anti-DC-ASGPR-MOG induced MOG-specific CD4+CD25+FOXP3+CD39+ regulatory lymphocytes and favoured an upsurge in systemic TGFβ and IL-8 upon rhMOG re-administration in vivo. Interpretation: We show that the delivery of an anti-DC-ASGPR-MOG allows antigen-specific adaptive immune modulation to prevent the breach of immune tolerance to MOG. Our findings pave the way for therapeutic vaccines for long-lasting remission to grave encephalomyelitis with identified autoantigens, such as ADD associated with anti-MOG autoantibodies. Fund: Work supported by the French ANR (ANR-11-INBS-0008 and ANR-10-EQPX-02-01), NIH (NIH 1 R01 AI 105066), the Baylor Scott and White Healthcare System funding and Roche Research Collaborative grants. Keywords: EAE, TGFβ, Tolerance, Treg, Anti-MOG IgG, Macaque |
| first_indexed | 2024-12-19T08:24:07Z |
| format | Article |
| id | doaj.art-8dcb23ba52be4f9b83ca67c40e294427 |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-12-19T08:24:07Z |
| publishDate | 2019-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-8dcb23ba52be4f9b83ca67c40e2944272022-12-21T20:29:21ZengElsevierEBioMedicine2352-39642019-09-0147492505Intradermal vaccination prevents anti-MOG autoimmune encephalomyelitis in macaquesResearch in contextClaire-Maëlle Fovet0Lev Stimmer1Vanessa Contreras2Philippe Horellou3Audrey Hubert4Nabila Seddiki5Catherine Chapon6Sabine Tricot7Carole Leroy8Julien Flament9Julie Massonneau10Nicolas Tchitchek11Bert A. 't Hart12Sandra Zurawski13Peter Klucar14Philippe Hantraye15Kumaran Deiva16Gerard Zurawski17SangKon Oh18Roger Le Grand19Ché Serguera20Commissariat à l'Énergie Atomique (CEA), Molecular Imaging Research Center (MIRCen), 92260 Fontenay-aux-Roses, FranceCommissariat à l'Énergie Atomique (CEA), Molecular Imaging Research Center (MIRCen), 92260 Fontenay-aux-Roses, FranceCEA, INSERM, Université Paris-Sud, U1184, IDMIT Department, Fontenay-aux-Roses 92265, FranceCEA, INSERM, Université Paris-Sud, U1184, IDMIT Department, Fontenay-aux-Roses 92265, FranceVacine Research Institute, INSERM U955 Institut Mondor de Recherche Biomédicale (IMRB), Créteil, FranceVacine Research Institute, INSERM U955 Institut Mondor de Recherche Biomédicale (IMRB), Créteil, FranceCEA, INSERM, Université Paris-Sud, U1184, IDMIT Department, Fontenay-aux-Roses 92265, FranceCEA, INSERM, Université Paris-Sud, U1184, IDMIT Department, Fontenay-aux-Roses 92265, FranceCEA, INSERM, Université Paris-Sud, U1184, IDMIT Department, Fontenay-aux-Roses 92265, FranceCommissariat à l'Énergie Atomique (CEA), Molecular Imaging Research Center (MIRCen), 92260 Fontenay-aux-Roses, FranceCommissariat à l'Énergie Atomique (CEA), Molecular Imaging Research Center (MIRCen), 92260 Fontenay-aux-Roses, France; Laboratoire des Biothérapies, INSERM, UMS27, F-92260 Fontenay-aux-Roses, FranceCEA, INSERM, Université Paris-Sud, U1184, IDMIT Department, Fontenay-aux-Roses 92265, FranceDepartment of Immunobiology, Biomedical Primate Research Centre (BPRC), 2280 GH Rijswijk, the Netherlands; University of Groningen, Department of Biomedical Sciences of Cells and Systems, University Medical Center, Groningen, the NetherlandsBaylor Institute for Immunology Research (BIIR), Dallas, TX 75204, USABaylor Institute for Immunology Research (BIIR), Dallas, TX 75204, USACommissariat à l'Énergie Atomique (CEA), Molecular Imaging Research Center (MIRCen), 92260 Fontenay-aux-Roses, FranceCEA, INSERM, Université Paris-Sud, U1184, IDMIT Department, Fontenay-aux-Roses 92265, FranceBaylor Institute for Immunology Research (BIIR), Dallas, TX 75204, USAMayo Clinic, Department of Immunology, Scottsdale, AZ 85259, USACEA, INSERM, Université Paris-Sud, U1184, IDMIT Department, Fontenay-aux-Roses 92265, FranceLaboratoire des Biothérapies, INSERM, UMS27, F-92260 Fontenay-aux-Roses, France; Asfalia Biologics, Institut du Cerveau et de la Moelle épinière (ICM), Hôpital Pitiè-Sâlpétrière, Paris 75013, France; Corresponding author at: Asfalia Biologics ICM, Hopital Pitié-Salpetrière, Paris 75013, FranceBackground: Autoimmune demyelinating diseases (ADD) are a major cause of neurological disability due to autoreactive cellular and humoral immune responses against brain antigens. A cure for chronic ADD could be obtained by appropriate immunomodulation. Methods: We implemented a preclinical scheme to foster immune tolerance to myelin oligodendrocyte glycoprotein (MOG), in a cynomolgus-macaque model of experimental autoimmune encephalomyelitis (EAE), in which administration of recombinant human MOG (rhMOG) elicits brain inflammation mediated by MOG-autoreactive CD4+ lymphocytes and anti-MOG IgG. For immunotherapy, we used a recombinant antibody (Ab) directed against the dendritic cell-asialoglycoprotein receptor (DC-ASGPR) fused either to MOG or a control antigen PSA (prostate-specific antigen). Findings: rhMOG and the anti-DC-ASGPR-MOG were respectively detected in CD1a+ DCs or CD163+ cells in the skin of macaques. Intradermal administration of anti-DC-ASGPR-MOG, but not control anti-DC-ASGPR-PSA, was protective against EAE. The treatment prevented the CD4+ T cell activation and proinflammatory cytokine production observed in controls. Moreover, the administration of anti-DC-ASGPR-MOG induced MOG-specific CD4+CD25+FOXP3+CD39+ regulatory lymphocytes and favoured an upsurge in systemic TGFβ and IL-8 upon rhMOG re-administration in vivo. Interpretation: We show that the delivery of an anti-DC-ASGPR-MOG allows antigen-specific adaptive immune modulation to prevent the breach of immune tolerance to MOG. Our findings pave the way for therapeutic vaccines for long-lasting remission to grave encephalomyelitis with identified autoantigens, such as ADD associated with anti-MOG autoantibodies. Fund: Work supported by the French ANR (ANR-11-INBS-0008 and ANR-10-EQPX-02-01), NIH (NIH 1 R01 AI 105066), the Baylor Scott and White Healthcare System funding and Roche Research Collaborative grants. Keywords: EAE, TGFβ, Tolerance, Treg, Anti-MOG IgG, Macaquehttp://www.sciencedirect.com/science/article/pii/S2352396419305742 |
| spellingShingle | Claire-Maëlle Fovet Lev Stimmer Vanessa Contreras Philippe Horellou Audrey Hubert Nabila Seddiki Catherine Chapon Sabine Tricot Carole Leroy Julien Flament Julie Massonneau Nicolas Tchitchek Bert A. 't Hart Sandra Zurawski Peter Klucar Philippe Hantraye Kumaran Deiva Gerard Zurawski SangKon Oh Roger Le Grand Ché Serguera Intradermal vaccination prevents anti-MOG autoimmune encephalomyelitis in macaquesResearch in context EBioMedicine |
| title | Intradermal vaccination prevents anti-MOG autoimmune encephalomyelitis in macaquesResearch in context |
| title_full | Intradermal vaccination prevents anti-MOG autoimmune encephalomyelitis in macaquesResearch in context |
| title_fullStr | Intradermal vaccination prevents anti-MOG autoimmune encephalomyelitis in macaquesResearch in context |
| title_full_unstemmed | Intradermal vaccination prevents anti-MOG autoimmune encephalomyelitis in macaquesResearch in context |
| title_short | Intradermal vaccination prevents anti-MOG autoimmune encephalomyelitis in macaquesResearch in context |
| title_sort | intradermal vaccination prevents anti mog autoimmune encephalomyelitis in macaquesresearch in context |
| url | http://www.sciencedirect.com/science/article/pii/S2352396419305742 |
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