Targeting VEGF-A with a vaccine decreases inflammation and joint destruction in experimental arthritis
| Autor: | Emilie Duvallet, Marie-Christophe Boissier, Nicolas Marival, Emilie Bernier, Nicolas Schall, Nadia Belmellat, Sylviane Muller, Maelle Monteil, Géraldine Grouard-Vogel, Marc Lecouvey, Hanna Hlawaty, Luca Semerano, Eric Assier |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Male Vascular Endothelial Growth Factor A Cancer Research Physiology medicine.medical_treatment Clinical Biochemistry Molecular Sequence Data Arthritis Inflammation 03 medical and health sciences chemistry.chemical_compound Mice Synovitis medicine Human Umbilical Vein Endothelial Cells Animals Humans Amino Acid Sequence Molecular Targeted Therapy Vaccines biology business.industry Synovial Membrane medicine.disease Arthritis Experimental 3. Good health Immunity Humoral Vascular endothelial growth factor 030104 developmental biology Cytokine medicine.anatomical_structure chemistry Immunology Antibody Formation Peptide vaccine biology.protein Immunization Joints Synovial membrane medicine.symptom business Peptides Keyhole limpet hemocyanin |
| Zdroj: | Angiogenesis. 19(1) |
| ISSN: | 1573-7209 |
| Popis: | 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). 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. 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. 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink