title: Suppressive DNA vaccination in myelin oligodendrocyte glycoprotein peptide-induced experimental autoimmune encephalomyelitis involves a T1-biased immune response.
abstract: Vaccination with DNA encoding a myelin basic protein peptide suppresses Lewis rat experimental autoimmune encephalomyelitis (EAE) induced with the same peptide. Additional myelin proteins, such as myelin oligodendrocyte glycoprotein (MOG), may be important in multiple sclerosis. Here we demonstrate that DNA vaccination also suppresses MOG peptide-induced EAE. MOG(91-108) is encephalitogenic in DA rats and MHC-congenic LEW.1AV1 (RT1(av1)) and LEW.1N (RT1(n)) rats. We examined the effects of DNA vaccines encoding MOG(91-108) in tandem, with or without targeting of the hybrid gene product to IgG. In all investigated rat strains DNA vaccination suppressed clinical signs of EAE. There was no requirement for targeting the gene product to IgG, but T1-promoting CpG DNA motifs in the plasmid backbone of the construct were necessary for efficient DNA vaccination, similar to the case in DNA vaccination in myelin basic protein-induced EAE. We failed to detect any effects on ex vivo MOG-peptide-induced IFN-gamma, TNF-alpha, IL-6, IL-4, IL-10, and brain-derived neurotropic factor expression in splenocytes or CNS-derived lymphocytes. In CNS-derived lymphocytes, Fas ligand expression was down-regulated in DNA-vaccinated rats compared with controls. However, MOG-specific IgG2b responses were enhanced after DNA vaccination. The enhanced IgG2b responses together with the requirement for CpG DNA motifs in the vaccine suggest a protective mechanism involving induction of a T1-biased immune response.
authors.affiliation: Neuroimmunology Unit, Center for Molecular Medicine, L8:04, Karolinska Hospital, 171 76 Stockholm, Sweden. anna.lobell@cmm.ki.se
authors.forename: Anna
authors.initials: A
authors.lastname: Lobell
authors.forename: Robert
authors.initials: R
authors.lastname: Weissert
authors.forename: Sana
authors.initials: S
authors.lastname: Eltayeb
authors.forename: Katrien L
authors.initials: KL
authors.lastname: de Graaf
authors.forename: Judit
authors.initials: J
authors.lastname: Wefer
authors.forename: Maria K
authors.initials: MK
authors.lastname: Storch
authors.forename: Hans
authors.initials: H
authors.lastname: Lassmann
authors.forename: Hans
authors.initials: H
authors.lastname: Wigzell
authors.forename: Tomas
authors.initials: T
authors.lastname: Olsson
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016175:B-Lymphocyte Subsets / Q000276:immunology; D002478:Cells, Cultured; D018899:CpG Islands / Q000276:immunology; D004269:DNA, Bacterial / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000401:mortality / Q000473:pathology / Q000517:prevention & control*; D005260:Female; D006168:Guinea Pigs; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000276:immunology*; D007273:Injections, Intramuscular; D051379:Mice; D008969:Molecular Sequence Data; D018992:Myelin-Associated Glycoprotein / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D016176:T-Lymphocyte Subsets / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
chemical_list: D004269:DNA, Bacterial; D007166:Immunosuppressive Agents; C442246:MOG peptide 97-108; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D019444:Vaccines, DNA