Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement
The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.
Active Immunization against VEGF Improves Joint Inflammation and Destruction in Collagen-Induced Arthritis
Assier1, Eric, Semerano2, Luca, Delavallee1, Laure, Grouard-Vogel3, Géraldine, Bernier3, Emilie, Zagury3, Daniel, Boissier2, Marie-Christophe
Cytokines play a key role in the development of rheumatoid arthritis (RA), allowing hypertrophy of the pannus by neovascularisation, articular inflammation and destruction. We recently demonstrated in experimental models the efficacy of vaccination against cytokines, using a heterocomplex of keyhole limpet hemocyanin (KLH) and human TNF, called TNF kinoid (K). VEGF is a potential target in RA, since it plays a major role in angiogenesis and pannus formation. We aimed at demonstrating an inhibitory effect of a sustained inhibition of VEGF by an anti-VEGF vaccine in collagen-induced-arthritis (CIA).
Anti-murine VEGF immunization was performed by injecting intra-muscularly VEGF-K formulated in incomplete Freund adjuvant (IFA) in DBA/1 mice. Control groups received KLH or PBS at the same dates. A fourth group received a chemical angiogenesis inhibitor in drinking water from D28 to sacrifice (Ammonium Tetrathiomolybdate, TM, 0.03mg/ml). Arthritides were induced by two subcutaneous injections of bovine type II collagen, the first at Day 40 in complete Freund adjuvant, the second at Day 61 in IFA. Clinical scores of arthritis were evaluated twice per week. Histological scores of the paws were quantified after sacrifice and Hematoxylin/Eosin staining. Anti-VEGF and anti-KLH antibody (Ab) levels were assessed by ELISA, and the anti-VEGF neutralizing capacity (NC) of sera by HUVEC bioassay.
VEGF-K and TM groups showed lower arthritic scores as compared to KLH and PBS groups (p<0.005). At histological analysis, inflammation and destruction scores of the paws were lower in VEGF-K group versus KLH (p<0.005) and PBS group (p<0.001). VEGF-K group was the only one to show anti-VEGF Ab production as assessed by ELISA at Day 60 and sacrifice. The neutralizing activity of anti-VEGF Ab was confirmed by HUVEC at sacrifice.
These data show that VEGF-K improves arthritis in a murine RA model.
To cite this abstract, please use the following information:
Assier, Eric, Semerano, Luca, Delavallee, Laure, Grouard-Vogel, Géraldine, Bernier, Emilie, Zagury, Daniel, et al; Active Immunization against VEGF Improves Joint Inflammation and Destruction in Collagen-Induced Arthritis [abstract]. Arthritis Rheum 2009;60 Suppl 10 :662