Intradermal vaccination prevents anti-MOG autoimmune encephalomyelitis in macaquesResearch in context
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
Affiliations
Claire-Maëlle Fovet
Commissariat à l'Énergie Atomique (CEA), Molecular Imaging Research Center (MIRCen), 92260 Fontenay-aux-Roses, France
Lev Stimmer
Commissariat à l'Énergie Atomique (CEA), Molecular Imaging Research Center (MIRCen), 92260 Fontenay-aux-Roses, France
Vanessa Contreras
CEA, INSERM, Université Paris-Sud, U1184, IDMIT Department, Fontenay-aux-Roses 92265, France
Philippe Horellou
CEA, INSERM, Université Paris-Sud, U1184, IDMIT Department, Fontenay-aux-Roses 92265, France
Audrey Hubert
Vacine Research Institute, INSERM U955 Institut Mondor de Recherche Biomédicale (IMRB), Créteil, France
Nabila Seddiki
Vacine Research Institute, INSERM U955 Institut Mondor de Recherche Biomédicale (IMRB), Créteil, France
Catherine Chapon
CEA, INSERM, Université Paris-Sud, U1184, IDMIT Department, Fontenay-aux-Roses 92265, France
Sabine Tricot
CEA, INSERM, Université Paris-Sud, U1184, IDMIT Department, Fontenay-aux-Roses 92265, France
Carole Leroy
CEA, INSERM, Université Paris-Sud, U1184, IDMIT Department, Fontenay-aux-Roses 92265, France
Julien Flament
Commissariat à l'Énergie Atomique (CEA), Molecular Imaging Research Center (MIRCen), 92260 Fontenay-aux-Roses, France
Julie Massonneau
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
Nicolas Tchitchek
CEA, INSERM, Université Paris-Sud, U1184, IDMIT Department, Fontenay-aux-Roses 92265, France
Bert A. 't Hart
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
Sandra Zurawski
Baylor Institute for Immunology Research (BIIR), Dallas, TX 75204, USA
Peter Klucar
Baylor Institute for Immunology Research (BIIR), Dallas, TX 75204, USA
Philippe Hantraye
Commissariat à l'Énergie Atomique (CEA), Molecular Imaging Research Center (MIRCen), 92260 Fontenay-aux-Roses, France
Kumaran Deiva
CEA, INSERM, Université Paris-Sud, U1184, IDMIT Department, Fontenay-aux-Roses 92265, France
Gerard Zurawski
Baylor Institute for Immunology Research (BIIR), Dallas, TX 75204, USA
SangKon Oh
Mayo Clinic, Department of Immunology, Scottsdale, AZ 85259, USA
Roger Le Grand
CEA, INSERM, Université Paris-Sud, U1184, IDMIT Department, Fontenay-aux-Roses 92265, France
Ché Serguera
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; Corresponding author at: Asfalia Biologics ICM, Hopital Pitié-Salpetrière, Paris 75013, France
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
