Session Title: Rheumatoid Arthritis - Animal Models II
Session Type: Abstract Submissions (ACR)
Background/Purpose: We have 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 plays a key role in the development of rheumatoid arthritis (RA), allowing hypertrophy of the pannus by neovascularisation, articular inflammation and destruction. Thus, VEGF is a potential target in RA.
We aimed at demonstrating an inhibitory effect of a sustained inhibition of VEGF by vaccines based on VEGF-derived peptides linked to KLH (Vpep-K) in collagen-induced-arthritis (CIA).
Methods: Anti-murine VEGF immunization was performed by injecting intra-muscularly Vpep1-K and Vpep2-K formulated in incomplete Freund adjuvant (IFA) in DBA/1 mice (at days -36, -22, -8, 7 and 37). Control groups received KLH or PBS on the same schedule. Arthritides were induced by two subcutaneous injections of bovine type II collagen, the first at day 0 in complete Freund adjuvant, the second at day 21 in IFA. Clinical scores of arthritis were evaluated twice per week. Histological scores of joint inflammation and destruction after Hematoxylin/Eosin staining were quantified at sacrifice. Anti-peptide, anti-VEGF and anti-KLH antibody (Ab) levels were assessed by ELISA.
Results: Vpep1-K group showed lower arthritic scores as compared to KLH and PBS groups (p<0.05). At histological analysis, inflammation and destruction scores of the paws were lower in Vpep1-K group versus KLH and PBS group (p<0.005). Vpep1-K and Vpep2-K groups induced anti-VEGF Ab production as assessed by ELISA at day -2 and sacrifice.
Conclusion: These data show that Vpep1-K induces anti-VEGF Abs and improves arthritis in a murine model of RA.
M. C. Boissier,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/active-immunization-against-vegf-derived-oligopeptides-improves-joint-inflammation-and-destruction-in-collagen-induced-arthritis/