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Inverse Vaccination to Silence Immunity to Myelin in Multiple Sclerosis

Published online by Cambridge University Press:  02 December 2014

Lawrence Steinman
Lawrence Steinman*
Affiliation:
Department of Neurological Sciences and Interdepartmental Program in Immunology, Stanford University, Stanford, California, USA.
*
Department of Neurological Sciences and Interdepartmental Program in Immunology, Stanford University, Stanford, California, 94305, USA.
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Abstract:

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The adaptive immune response in multiple sclerosis is complex. We have devised large scale arrays to measure the antibody response to myelin proteins and lipids. Despite the widespread immune responses to myelin, we have devised an inverse vaccine aimed at turning off key drivers of this diverse response. Clinical trials in patients with multiple sclerosis show that it is possible to constrain antibody responses to myelin on a large scale with this approach.

Résumé:

RÉSUMÉ:

La réponse immunitaire d'adaptation dans la sclérose en plaques est complexe. Nous avons créé des biopuces pour mesurer la réponse immunitaire aux protéines et aux lipides de la myéline. Même si la réponse immunitaire à la myéline est largement répandue, nous avons conçu un vaccin inverse dans le but d'abolir les éléments nourriciers clés de cette réponse hétérogène. Des essais cliniques chez des patients atteints de sclérose en plaques ont montré qu'il est possible de réprimer la production d'anticorps dirigés contre la myéline sur une grande échelle en utilisant cette approche.

Type
Research Article
Information
Canadian Journal of Neurological Sciences , Volume 37 , supplement S2 , September 2010 , pp. S49 - S58
Copyright
Copyright © Canadian Neurological Sciences Federation 2010

References

1. Sercarz, EE. Arraying autoimmunity treatment. Nat Biotechnol. 2003; 21: 1017–9.Google Scholar
2. Lehmann, PV, Forsthuber, T, Miller, A, et al. Spreading of T-cell autoimmunity to cryptic determinants of an autoantigen. Nature. 1992; 358: 155–7.Google Scholar
3. Kanter, J, Narayana, S, Ho, P, et al. Lipid microarrays identify key mediators of autoimmune brain inflammation. Nat Med. 2006; 12: 138–43.CrossRefGoogle ScholarPubMed
4. Ousman, SS, Tomooka, BH, Van Noort, JM, et al. Protective and therapeutic role for aB-Crystallin in autoimmune demyelination. Nature. 2007; 448: 474–9.CrossRefGoogle Scholar
5. Ransohoff, RM, Inflammatory disease: assault against the guardian. Nature. 2007; 448: 421–2.Google Scholar
6. Jenner, E. The three original publications on vaccination against smallpox by Edward Jenner.In: Harvard Classics. NewYork: PF Collier & Son; 1910. vol.38.Google Scholar
7. Polman, CH, O’Connor, PW, Havrdova, E, et al. A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med. 2006; 354: 899–910.Google Scholar
8. Langer-Gould, A, Atlas, AJ, et al. Progressive multifocal leukoencephalopathy in a patient treated with natalizumab. N Engl J Med. 2005; 353: 375–81.Google Scholar
9. Steinman, L. Blocking adhesion molecules as therapy for multiple sclerosis: Natalizumab. Nature Reviews Drug Discovery. 2005; 4: 510–9.Google Scholar
10. Hauser, SL, Waubant, DL, et al. B-cell depletion with Riutximab in relapsing-remitting multiple sclerosis. N Engl J Med. 2009; 358: 676–88.Google Scholar
11. FDA public health advisory: life-threatening brain infection in patients with systemic lupus erythematosus after Rituxan (rituximab) treatment. Rockville, MD: Food and Drug Administration, 2006. [updated 2010 January 21; cited 2008 January 18]. Available from: Google Scholar
12. The CAMMS223 Trial Investigators.Alemtuzumab vs. interferon beta-1a in early multiple sclerosis. N Engl J Med. 2008; 359: 1786–801.Google Scholar
13. Coles, AJ, Wing, M, Smith, S, et al. Pulsed monoclonal antibody treatment and autoimmune thyroid disease in multiple sclerosis. Lancet. 1999; 354: 1691–5.CrossRefGoogle ScholarPubMed
14. Robinson, WH, Fontoura, P, Lee, BJ, et al. Reverse genomics: Protein microarrays guide tolerizing DNA vaccine treatment of autoimmune encephalomyelitis, Nat Biotechnol. 2003; 21: 1033–9.Google Scholar
15. Steinman, L. The gray aspects of white matter disease in multiple sclerosis. Proc Natl Acad Sci U S A. 2009; 106: 8083–4.Google Scholar
16. Derfuss, T, Parikh, K, Velhin, S, et al. Contactin-2/Tag-1 directed autoimmunity is identified in multiple sclerosis and mediates gray matter pathology in animals. Proc Natl Acad Sci USA. 2009; 106: 8302–7.CrossRefGoogle Scholar
17. Mathey, EK, Derfuss, T, Storch, MK, et al. Neurofascin as a novel target for autoantibody-mediated axonal injury J Exp Med.Oct 2007; 204: 2363–72.Google Scholar
18. Sakai, K, Sinha, A, Mitchell, DJ, et al. Involvement of distinct T cell receptors in the autoimmune encephalitogenic response to nested epitopes of myelin basic protein. Proc Natl Acad Sci USA. 1988; 85: 8608–12.CrossRefGoogle ScholarPubMed
19. Zamvil, S, Mitchell, D, Powell, M, et al. Multiple discrete epitopes of the autoantigen myelin basic protein. J Exp Med. 1988; 168: 1181–6.CrossRefGoogle ScholarPubMed
20. Warren, KG, Catz, I, Steinman, L. Fine specificity of the antibody response to myelin basic protein in the central nervous system in multiple sclerosis: The minimal B cell epitope and a model of its unique features. Proc Natl Acad Sci USA. 1995; 92: 11061–5.Google Scholar
21. Ho, P, Fontoura, P, Ruiz, P, et al. Ani GpG oligonucleotide for the treatment of autoimmunity via the innate and adaptive immune systems. J Immunol. 2003; 171: 4920–6.Google Scholar
22. Ho, P, Platten, M, et al. A suppressive oligodeoxynucleotide enhances the efficacy of myelin cocktail/IL-4 tolerizing DNA vaccination and treats autoimmune disease. J Immunol. 2005; 175: 6226–34.CrossRefGoogle ScholarPubMed
23. Bar-Or, A, Vollmer, T, Antel, J, et al. Induction of antigen-specific tolerance in multiple sclerosis after immunization with DNA encoding myelin basic protein in a randomized, placebocontrolled phase 1-2 trial. Arch Neurol. 2007; 64: 1407–15.Google Scholar
24. Youssef, S, Stuve, O, Patorroyo, J, et al. The HMG-CoA reductase inhibitor, Atorvastatin, promotes a Th2 bias and reverses paralysis in CNS autoimmune disease. Nature. 2002; 420: 78–84.CrossRefGoogle Scholar
25. Garren, H, Robinson, W, Krasulová, E, et al. Phase 2b trial of a DNA vaccine encoding myelin basic protein in relapsing multiple sclerosis. Ann Neurol. 2008; 63 (5): 611–20.Google Scholar