Format

Send to

Choose Destination

See 1 citation found by title matching your search:

EBioMedicine. 2019 Sep;47:492-505. doi: 10.1016/j.ebiom.2019.08.052. Epub 2019 Sep 3.

Intradermal vaccination prevents anti-MOG autoimmune encephalomyelitis in macaques.

Author information

1
Commissariat à l'Énergie Atomique (CEA), Molecular Imaging Research Center (MIRCen), 92260 Fontenay-aux-Roses, France.
2
CEA, INSERM, Université Paris-Sud, U1184, IDMIT Department, Fontenay-aux-Roses 92265, France.
3
Vacine Research Institute, INSERM U955 Institut Mondor de Recherche Biomédicale (IMRB), Créteil, France.
4
Commissariat 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, France.
5
Department 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 Netherlands.
6
Baylor Institute for Immunology Research (BIIR), Dallas, TX 75204, USA.
7
Mayo Clinic, Department of Immunology, Scottsdale, AZ 85259, USA.
8
Laboratoire 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. Electronic address: che.serguera-y-lagache@inserm.fr.

Abstract

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:

Anti-MOG IgG; EAE; Macaque; TGFβ; Tolerance; Treg

PMID:
31492559
DOI:
10.1016/j.ebiom.2019.08.052
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center