27/02/2013 1 EAE IDDM
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27/02/2013 EAE IDDM Immunizing transgenes • Insulin B chain (plasmid) • IgFc-GAD65 (plasmid, retrovirus), spGAD65 (plasmid) • hsp60 (plasmid) 1 27/02/2013 IDDM Immunodeviation IgFc-GAD65 IL10 spGAD65 EXPERIMENTAL ARTHRITIS Immunizing transgenes • Collagen type II (plasmid) • C-C chemokines: MCP-1, MIP-1a, MIP-1b, RANTES (plasmid) • TNFa (plasmid) 2 27/02/2013 EXPERIMENTAL ARTHRITIS Neutralizing antibodies Table 1. Protocols of DNA vaccination applied succesfully to experimental autoimmune diseases Disease Antigenic target EAE TCR Vb 8.2 MBP PLP MOG IDDM Insulin GAD65 Soluble GAD65 Hsp60 Arthritis Vector Plasmid and viral (adenovirus, vaccinia virus) Plasmid Plasmid Plasmid Associated molecules Induced pathway of immune response Reference N. None IgG-binding ZZ protein None; IL-4 None Th1 activating Th2 Th1 activating Th2 Th1 to Th2 immunodeviation Th1 22,23,24 25 26 27 Plasmid Plasmid and virus (r) Plasmid Plasmid None (LCMV mice); IL-4 (NOD mice) Ig-Fc or IL-4 None; Bax None Th1 to Th2 immunodeviation, induction of Tregs Th1 to Th2 immunodeviation Th1 to Th2 immunodeviation, Treg activation (CD4+CD25+) Th1 to Th2 immunodeviation 29,30,32,33 28-34 35 36 Collagen type II C-C chemokines TNFa Plasmid Plasmid Plasmid IL-4 None None Th1 to Th2 immunodeviation Neutralizing antibodies Neutralizing antibodies 37 39 40 Uveitis Protein S Viral vector (retrovirus) None Undetermined 42 SLE Consensus peptide (pCons) Plasmid None Induction of T suppressors (CD8+CD28-) Antiphospholipid syndrome TNFa Plasmid None Neutralizing antibodies F.Ferrera et al 41 3 27/02/2013 SLE NUCLEOSOME 4 27/02/2013 5 27/02/2013 IDIOTYPIC NETWORK IN SLE Anti-dsDNA Abs Treg pCons pCons: a consensus peptide derived from immunogenic sequences from variable regions of different anti-dsDNA mAbs. 6 27/02/2013 EcoRI EcoRI XbaI pIgCons plasmid ATG pCMV hIgG1 Fc pNEG hIgG1 Fc EcoRI EcoRI XbaI pIgNeg plasmid pCONS ATG pCMV EcoRI XbaI EcoRI pIg plasmid ATG pCMV hIgG1 Fc 7 27/02/2013 Somatic transgene immunization B Fc pCons B 8
