Intradermal vaccination prevents anti-MOG autoimmune encephalomyelitis in macaques

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

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.

MeSH terms

  • Animals
  • Autoantibodies / immunology*
  • Autoantigens / immunology*
  • Cytokines / metabolism
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Encephalomyelitis, Autoimmune, Experimental / diagnosis
  • Encephalomyelitis, Autoimmune, Experimental / prevention & control*
  • Humans
  • Lymphocytes / immunology
  • Lymphocytes / metabolism
  • Macaca
  • Myelin-Oligodendrocyte Glycoprotein / antagonists & inhibitors
  • Myelin-Oligodendrocyte Glycoprotein / immunology*
  • Phenotype
  • Recombinant Proteins
  • Vaccination
  • Vaccines / administration & dosage
  • Vaccines / immunology*

Substances

  • Autoantibodies
  • Autoantigens
  • Cytokines
  • MOG protein, human
  • Myelin-Oligodendrocyte Glycoprotein
  • Recombinant Proteins
  • Vaccines