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Intradermal vaccination prevents anti-MOG autoimmune encephalomyelitis in macaques
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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6796575/ https://www.ncbi.nlm.nih.gov/pubmed/31492559 http://dx.doi.org/10.1016/j.ebiom.2019.08.052 |
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author | Fovet, Claire-Maëlle Stimmer, Lev Contreras, Vanessa Horellou, Philippe Hubert, Audrey Seddiki, Nabila Chapon, Catherine Tricot, Sabine Leroy, Carole Flament, Julien Massonneau, Julie Tchitchek, Nicolas 't Hart, Bert A. Zurawski, Sandra Klucar, Peter Hantraye, Philippe Deiva, Kumaran Zurawski, Gerard Oh, SangKon Le Grand, Roger Serguera, Ché |
author_facet | Fovet, Claire-Maëlle Stimmer, Lev Contreras, Vanessa Horellou, Philippe Hubert, Audrey Seddiki, Nabila Chapon, Catherine Tricot, Sabine Leroy, Carole Flament, Julien Massonneau, Julie Tchitchek, Nicolas 't Hart, Bert A. Zurawski, Sandra Klucar, Peter Hantraye, Philippe Deiva, Kumaran Zurawski, Gerard Oh, SangKon Le Grand, Roger Serguera, Ché |
author_sort | Fovet, Claire-Maëlle |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-6796575 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-67965752019-10-22 Intradermal vaccination prevents anti-MOG autoimmune encephalomyelitis in macaques Fovet, Claire-Maëlle Stimmer, Lev Contreras, Vanessa Horellou, Philippe Hubert, Audrey Seddiki, Nabila Chapon, Catherine Tricot, Sabine Leroy, Carole Flament, Julien Massonneau, Julie Tchitchek, Nicolas 't Hart, Bert A. Zurawski, Sandra Klucar, Peter Hantraye, Philippe Deiva, Kumaran Zurawski, Gerard Oh, SangKon Le Grand, Roger Serguera, Ché EBioMedicine Research paper 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. Elsevier 2019-09-03 /pmc/articles/PMC6796575/ /pubmed/31492559 http://dx.doi.org/10.1016/j.ebiom.2019.08.052 Text en © 2019 The Authors. Published by Elsevier B.V. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Research paper Fovet, Claire-Maëlle Stimmer, Lev Contreras, Vanessa Horellou, Philippe Hubert, Audrey Seddiki, Nabila Chapon, Catherine Tricot, Sabine Leroy, Carole Flament, Julien Massonneau, Julie Tchitchek, Nicolas 't Hart, Bert A. Zurawski, Sandra Klucar, Peter Hantraye, Philippe Deiva, Kumaran Zurawski, Gerard Oh, SangKon Le Grand, Roger Serguera, Ché Intradermal vaccination prevents anti-MOG autoimmune encephalomyelitis in macaques |
title | Intradermal vaccination prevents anti-MOG autoimmune encephalomyelitis in macaques |
title_full | Intradermal vaccination prevents anti-MOG autoimmune encephalomyelitis in macaques |
title_fullStr | Intradermal vaccination prevents anti-MOG autoimmune encephalomyelitis in macaques |
title_full_unstemmed | Intradermal vaccination prevents anti-MOG autoimmune encephalomyelitis in macaques |
title_short | Intradermal vaccination prevents anti-MOG autoimmune encephalomyelitis in macaques |
title_sort | intradermal vaccination prevents anti-mog autoimmune encephalomyelitis in macaques |
topic | Research paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6796575/ https://www.ncbi.nlm.nih.gov/pubmed/31492559 http://dx.doi.org/10.1016/j.ebiom.2019.08.052 |
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