title: Targeting VEGF-A with a vaccine decreases inflammation and joint destruction in experimental arthritis.
abstract: OBJECTIVE
  Inflammation and angiogenesis are two tightly linked processes in arthritis, and therapeutic targeting of pro-angiogenic factors may contribute to control joint inflammation and synovitis progression. In this work, we explored whether vaccination against vascular endothelial growth factor (VEGF) ameliorates collagen-induced arthritis (CIA).
  
  
  METHODS
  Anti-VEGF vaccines were heterocomplexes consisting of the entire VEGF cytokine (or a VEGF-derived peptide) linked to the carrier protein keyhole limpet hemocyanin (KLH). Two kinds of vaccines were separately tested in two independent experiments of CIA. In the first, we tested a kinoid of the murine cytokine VEGF (VEGF-K), obtained by conjugating VEGF-A to KLH. For the second, we selected two VEGF-A-derived peptide sequences to produce heterocomplexes (Vpep1-K and Vpep2-K). DBA/1 mice were immunized with either VEGF-K, Vpep1-K, or Vpep2-K, before CIA induction. Clinical and histological scores of arthritis, anti-VEGF, anti-Vpep Ab titers, and anti-VEGF Abs neutralizing capacity were determined.
  
  
  RESULTS
  Both VEGF-K and Vpep1-K significantly ameliorated clinical arthritis scores and reduced synovial inflammation and joint destruction at histology. VEGF-K significantly reduced synovial vascularization. None of the vaccines reduced anti-collagen Ab response in mice. Both VEGF-K and Vpep1-K induced persistently high titers of anti-VEGF Abs capable of inhibiting VEGF-A bioactivity.
  
  
  CONCLUSIONS
  Vaccination against the pro-angiogenic factor VEGF-A leads to the production of anti-VEGF polyclonal Abs and has a significant anti-inflammatory effect in CIA. Restraining Ab response to a single peptide sequence (Vpep1) with a peptide vaccine effectively protects immunized mice from joint inflammation and destruction.
authors.affiliation: Inserm UMR 1125, Sorbonne Paris Cité - Université Paris 13, 74, rue Marcel Cachin, 93017, Bobigny, France. luca.semerano@avc.aphp.fr.|Sorbonne Paris Cité - Université Paris 13, 74 rue Marcel Cachin, 93000, Bobigny, France. luca.semerano@avc.aphp.fr.|Service de Rhumatologie, Assistance Publique - Hôpitaux de Paris (AP-HP) Groupe hospitalier Avicenne - Jean Verdier - René Muret, 125 rue de Stalingrad, 93000, Bobigny, France. luca.semerano@avc.aphp.fr.
authors.forename: Luca
authors.initials: L
authors.lastname: Semerano
authors.affiliation: Inserm UMR 1125, Sorbonne Paris Cité - Université Paris 13, 74, rue Marcel Cachin, 93017, Bobigny, France. duvallet.emilie@gmail.com.|Sorbonne Paris Cité - Université Paris 13, 74 rue Marcel Cachin, 93000, Bobigny, France. duvallet.emilie@gmail.com.
authors.forename: Emilie
authors.initials: E
authors.lastname: Duvallet
authors.affiliation: Inserm UMR 1125, Sorbonne Paris Cité - Université Paris 13, 74, rue Marcel Cachin, 93017, Bobigny, France. belmellat.nadia@univ-paris13.fr.|Sorbonne Paris Cité - Université Paris 13, 74 rue Marcel Cachin, 93000, Bobigny, France. belmellat.nadia@univ-paris13.fr.
authors.forename: Nadia
authors.initials: N
authors.lastname: Belmellat
authors.affiliation: Sorbonne Paris Cité - Université Paris 13, 74 rue Marcel Cachin, 93000, Bobigny, France. nmarinval@yahoo.fr.|Inserm UMR 1148, 74 rue Marcel Cachin, 93000, Bobigny, France. nmarinval@yahoo.fr.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Marival
authors.affiliation: CNRS, Immunopathologie et chimie thérapeutique/Laboratory of excellence Medalis, Institut de Biologie Moléculaire et Cellulaire, 15 rue René Descartes, 67000, Strasbourg, France. N.Schall@ibmc-cnrs.unistra.fr.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Schall
authors.affiliation: Sorbonne Paris Cité - Université Paris 13, 74 rue Marcel Cachin, 93000, Bobigny, France. maelle.monteil@univ-paris13.fr.|CNRS UMR 7244, 74 rue Marcel Cachin, 93000, Bobigny, France. maelle.monteil@univ-paris13.fr.
authors.forename: Maëlle
authors.initials: M
authors.lastname: Monteil
authors.affiliation: Néovacs SA, 14 Impasse Reille, 75014, Paris, France. gvogel@neovacs.com.
authors.forename: Géraldine
authors.initials: G
authors.lastname: Grouard-Vogel
authors.affiliation: Néovacs SA, 14 Impasse Reille, 75014, Paris, France. ebernier@neovacs.com.
authors.forename: Emilie
authors.initials: E
authors.lastname: Bernier
authors.affiliation: Sorbonne Paris Cité - Université Paris 13, 74 rue Marcel Cachin, 93000, Bobigny, France. marc.lecouvey@univ-paris13.fr.|CNRS UMR 7244, 74 rue Marcel Cachin, 93000, Bobigny, France. marc.lecouvey@univ-paris13.fr.
authors.forename: Marc
authors.initials: M
authors.lastname: Lecouvey
authors.affiliation: Sorbonne Paris Cité - Université Paris 13, 74 rue Marcel Cachin, 93000, Bobigny, France. h.hlawaty@smbh.univ-paris13.fr.|Inserm UMR 1148, 74 rue Marcel Cachin, 93000, Bobigny, France. h.hlawaty@smbh.univ-paris13.fr.
authors.forename: Hanna
authors.initials: H
authors.lastname: Hlawaty
authors.affiliation: CNRS, Immunopathologie et chimie thérapeutique/Laboratory of excellence Medalis, Institut de Biologie Moléculaire et Cellulaire, 15 rue René Descartes, 67000, Strasbourg, France. s.muller@ibmc-cnrs.unistra.fr.
authors.forename: Sylviane
authors.initials: S
authors.lastname: Muller
authors.affiliation: Inserm UMR 1125, Sorbonne Paris Cité - Université Paris 13, 74, rue Marcel Cachin, 93017, Bobigny, France. marie-christophe.boissier@avc.aphp.fr.|Sorbonne Paris Cité - Université Paris 13, 74 rue Marcel Cachin, 93000, Bobigny, France. marie-christophe.boissier@avc.aphp.fr.|Service de Rhumatologie, Assistance Publique - Hôpitaux de Paris (AP-HP) Groupe hospitalier Avicenne - Jean Verdier - René Muret, 125 rue de Stalingrad, 93000, Bobigny, France. marie-christophe.boissier@avc.aphp.fr.
authors.forename: Marie-Christophe
authors.initials: MC
authors.lastname: Boissier
authors.affiliation: Inserm UMR 1125, Sorbonne Paris Cité - Université Paris 13, 74, rue Marcel Cachin, 93017, Bobigny, France. eric.assier@univ-paris13.fr.|Sorbonne Paris Cité - Université Paris 13, 74 rue Marcel Cachin, 93000, Bobigny, France. eric.assier@univ-paris13.fr.
authors.forename: Eric
authors.initials: E
authors.lastname: Assier
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D001169:Arthritis, Experimental / Q000276:immunology* / Q000473:pathology; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D056724:Immunity, Humoral / Q000276:immunology; D007114:Immunization; D007249:Inflammation / Q000473:pathology*; D007596:Joints / Q000473:pathology*; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D058990:Molecular Targeted Therapy; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D013583:Synovial Membrane / Q000098:blood supply / Q000473:pathology; D014612:Vaccines / Q000276:immunology*; D042461:Vascular Endothelial Growth Factor A / Q000737:chemistry / Q000276:immunology*
chemical_list: D010455:Peptides; D014612:Vaccines; D042461:Vascular Endothelial Growth Factor A
keywords: Arthritis; Inflammation; Peptides; VEGF; Vaccines