Protein microarrays guide, tolerizing DNA vaccine treatment of autoimmune encephalomyelitis

William H. Robinson, Paulo Fontoura, Byung J. Lee, Henry E Neuman De Vegvar, Jennifer Tom, Rosetta Pedotti, Carla D. DiGennaro, Dennis J. Mitchell, Derek Fong, Peggy P K Ho, Pedro J. Ruiz, Emanual Maverakis, David B. Stevens, Claude C A Bernard, Roland Martin, Vijay K. Kuchroo, Johannes M. Van Noort, Claude P. Genain, Sandra Amor, Tomas OlssonPaul J. Utz, Hideki Garren, Lawrence Steinman

Research output: Contribution to journalArticle

Abstract

The diversity of autoimmune responses poses a formidable challenge to the development of antigen-specific tolerizing therapy. We developed 'myelin proteome' microarrays to profile the evolution of autoantibody responses in experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis (MS). Increased diversity of autoantibody responses in acute EAE predicted a more severe clinical course. Chronic EAE was associated with previously undescribed extensive intra- and intermolecular epitope spreading of autoreactive B-cell responses. Array analysis of autoantigens targeted in acute EAE was used to guide the choice of autoantigen cDNAs to be incorporated into expression plasmids so as to generate tolerizing vaccines. Tolerizing DNA vaccines encoding a greater number of array-determined myelin targets proved superior in treating established EAE and reduced epitope spreading of autoreactive B-cell responses. Proteomic monitoring of autoantibody responses provides a useful approach to monitor autoimmune disease and to develop and tailor disease- and patient-specific tolerizing DNA vaccines.

Original languageEnglish
Pages (from-to)1033-1039
Number of pages7
JournalNature Biotechnology
Volume21
Issue number9
DOIs
Publication statusPublished - Sep 1 2003

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Encephalomyelitis
Protein Array Analysis
DNA Vaccines
Autoimmune Experimental Encephalomyelitis
Microarrays
Autoantibodies
Epitopes
Autoantigens
Proteins
Cells
Myelin Sheath
Vaccines
Proteome
Antigens
B-Lymphocytes
Plasmids
Therapeutics
Complementary DNA
Autoimmunity
Monitoring

ASJC Scopus subject areas

  • Microbiology

Cite this

Robinson, W. H., Fontoura, P., Lee, B. J., De Vegvar, H. E. N., Tom, J., Pedotti, R., ... Steinman, L. (2003). Protein microarrays guide, tolerizing DNA vaccine treatment of autoimmune encephalomyelitis. Nature Biotechnology, 21(9), 1033-1039. https://doi.org/10.1038/nbt859

Protein microarrays guide, tolerizing DNA vaccine treatment of autoimmune encephalomyelitis. / Robinson, William H.; Fontoura, Paulo; Lee, Byung J.; De Vegvar, Henry E Neuman; Tom, Jennifer; Pedotti, Rosetta; DiGennaro, Carla D.; Mitchell, Dennis J.; Fong, Derek; Ho, Peggy P K; Ruiz, Pedro J.; Maverakis, Emanual; Stevens, David B.; Bernard, Claude C A; Martin, Roland; Kuchroo, Vijay K.; Van Noort, Johannes M.; Genain, Claude P.; Amor, Sandra; Olsson, Tomas; Utz, Paul J.; Garren, Hideki; Steinman, Lawrence.

In: Nature Biotechnology, Vol. 21, No. 9, 01.09.2003, p. 1033-1039.

Research output: Contribution to journalArticle

Robinson, WH, Fontoura, P, Lee, BJ, De Vegvar, HEN, Tom, J, Pedotti, R, DiGennaro, CD, Mitchell, DJ, Fong, D, Ho, PPK, Ruiz, PJ, Maverakis, E, Stevens, DB, Bernard, CCA, Martin, R, Kuchroo, VK, Van Noort, JM, Genain, CP, Amor, S, Olsson, T, Utz, PJ, Garren, H & Steinman, L 2003, 'Protein microarrays guide, tolerizing DNA vaccine treatment of autoimmune encephalomyelitis', Nature Biotechnology, vol. 21, no. 9, pp. 1033-1039. https://doi.org/10.1038/nbt859
Robinson WH, Fontoura P, Lee BJ, De Vegvar HEN, Tom J, Pedotti R et al. Protein microarrays guide, tolerizing DNA vaccine treatment of autoimmune encephalomyelitis. Nature Biotechnology. 2003 Sep 1;21(9):1033-1039. https://doi.org/10.1038/nbt859
Robinson, William H. ; Fontoura, Paulo ; Lee, Byung J. ; De Vegvar, Henry E Neuman ; Tom, Jennifer ; Pedotti, Rosetta ; DiGennaro, Carla D. ; Mitchell, Dennis J. ; Fong, Derek ; Ho, Peggy P K ; Ruiz, Pedro J. ; Maverakis, Emanual ; Stevens, David B. ; Bernard, Claude C A ; Martin, Roland ; Kuchroo, Vijay K. ; Van Noort, Johannes M. ; Genain, Claude P. ; Amor, Sandra ; Olsson, Tomas ; Utz, Paul J. ; Garren, Hideki ; Steinman, Lawrence. / Protein microarrays guide, tolerizing DNA vaccine treatment of autoimmune encephalomyelitis. In: Nature Biotechnology. 2003 ; Vol. 21, No. 9. pp. 1033-1039.
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