Intradermal vaccination prevents anti-MOG autoimmune encephalomyelitis in macaques

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 GrandChé Serguera

Research output: Contribution to journalArticle

1 Citation (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)492-505
Number of pages14
JournalEBioMedicine
Volume47
DOIs
StatePublished - Sep 1 2019

Fingerprint

Myelin-Oligodendrocyte Glycoprotein
Encephalomyelitis
Macaca
Vaccination
Asialoglycoprotein Receptor
Dendritic Cells
Demyelinating Diseases
Autoimmune Diseases
Immune Tolerance
Autoimmune Experimental Encephalomyelitis
Lymphocytes
Prostate-Specific Antigen
Antigens
Brain
T-cells
Immunomodulation
Organized Financing
Autoantigens
Encephalitis
Humoral Immunity

Keywords

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

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Fovet, C. M., Stimmer, L., Contreras, V., Horellou, P., Hubert, A., Seddiki, N., ... Serguera, C. (2019). Intradermal vaccination prevents anti-MOG autoimmune encephalomyelitis in macaques. EBioMedicine, 47, 492-505. https://doi.org/10.1016/j.ebiom.2019.08.052

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.

In: EBioMedicine, Vol. 47, 01.09.2019, p. 492-505.

Research output: Contribution to journalArticle

Fovet, CM, Stimmer, L, Contreras, V, Horellou, P, Hubert, A, Seddiki, N, Chapon, C, Tricot, S, Leroy, C, Flament, J, Massonneau, J, Tchitchek, N, 't Hart, BA, Zurawski, S, Klucar, P, Hantraye, P, Deiva, K, Zurawski, G, Oh, S, Le Grand, R & Serguera, C 2019, 'Intradermal vaccination prevents anti-MOG autoimmune encephalomyelitis in macaques', EBioMedicine, vol. 47, pp. 492-505. https://doi.org/10.1016/j.ebiom.2019.08.052
Fovet CM, Stimmer L, Contreras V, Horellou P, Hubert A, Seddiki N et al. Intradermal vaccination prevents anti-MOG autoimmune encephalomyelitis in macaques. EBioMedicine. 2019 Sep 1;47:492-505. https://doi.org/10.1016/j.ebiom.2019.08.052
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. In: EBioMedicine. 2019 ; Vol. 47. pp. 492-505.
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AU - Stimmer, Lev

AU - Contreras, Vanessa

AU - Horellou, Philippe

AU - Hubert, Audrey

AU - Seddiki, Nabila

AU - Chapon, Catherine

AU - Tricot, Sabine

AU - Leroy, Carole

AU - Flament, Julien

AU - Massonneau, Julie

AU - Tchitchek, Nicolas

AU - 't Hart, Bert A.

AU - Zurawski, Sandra

AU - Klucar, Peter

AU - Hantraye, Philippe

AU - Deiva, Kumaran

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AU - Le Grand, Roger

AU - Serguera, Ché

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N2 - 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.

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