title: DNA vaccine encoding CD40 targeted to dendritic cells in situ prevents the development of Heymann nephritis in rats.
abstract: The CD40-CD154 costimulatory pathway has been shown to be critical for both T- and B-cell activation in autoimmune disease. Here, we assessed the effects of blocking this pathway using CD40 DNA vaccine enhanced by dendritic cell targeting on the development of active Heymann nephritis, a rat model of human membranous nephropathy. DNA vaccination delivers plasmid DNA encoding the target antigen, either alone or in combination with enhancing elements, to induce both humoral and cellular immune responses. To determine whether CD40 DNA vaccine targeting the encoded CD40 directly to dendritic cells would improve the efficacy of the vaccination against self-protein CD40, we utilized a plasmid encoding a single-chain Fv antibody specific for the dendritic cell-restricted antigen-uptake receptor DEC205 (scDEC), the target gene CD40, and the adjuvant tetanus sequence p30. This vaccine plasmid was compared to a control plasmid without scDEC. Rats vaccinated with scDEC-CD40 had significantly less proteinuria and renal injury than did rats receiving scControl-CD40 and were protected from developing Heymann nephritis. Thus, CD40 DNA vaccination targeted to dendritic cells limits the development of Heymann nephritis.
authors.affiliation: Centre for Transplantation and Renal Research, University of Sydney at Westmead Millennium Institute, Westmead, Sydney, New South Wales, Australia.
authors.forename: Ya
authors.initials: Y
authors.lastname: Wang
authors.forename: Yuan Min
authors.initials: YM
authors.lastname: Wang
authors.forename: Yiping
authors.initials: Y
authors.lastname: Wang
authors.forename: Guoping
authors.initials: G
authors.lastname: Zheng
authors.forename: Geoff Yu
authors.initials: GY
authors.lastname: Zhang
authors.forename: Jimmy Jianheng
authors.initials: JJ
authors.lastname: Zhou
authors.forename: Thian Kui
authors.initials: TK
authors.lastname: Tan
authors.forename: Qi
authors.initials: Q
authors.lastname: Cao
authors.forename: Min
authors.initials: M
authors.lastname: Hu
authors.forename: Debbie
authors.initials: D
authors.lastname: Watson
authors.forename: Huiling
authors.initials: H
authors.lastname: Wu
authors.forename: Dong
authors.initials: D
authors.lastname: Zheng
authors.forename: ChangQi
authors.initials: C
authors.lastname: Wang
authors.forename: Mireille H
authors.initials: MH
authors.lastname: Lahoud
authors.forename: Irina
authors.initials: I
authors.lastname: Caminschi
authors.forename: David C
authors.initials: DC
authors.lastname: Harris
authors.forename: Stephen I
authors.initials: SI
authors.lastname: Alexander
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000097:blood; D019013:CD40 Antigens / Q000235:genetics* / Q000276:immunology / Q000502:physiology; D023201:CD40 Ligand / Q000502:physiology; D060908:CTLA-4 Antigen / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology*; D015433:Glomerulonephritis, Membranous / Q000517:prevention & control*; D007074:Immunoglobulin G / Q000378:metabolism; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D051381:Rats; D011917:Rats, Inbred Lew; D057127:Single-Chain Antibodies / Q000235:genetics; D014611:Vaccination; D019444:Vaccines, DNA / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D019013:CD40 Antigens; D060908:CTLA-4 Antigen; D007074:Immunoglobulin G; D057127:Single-Chain Antibodies; D019444:Vaccines, DNA; D023201:CD40 Ligand