Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement
The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.
A Therapeutic Vaccine Arrests Disease Progression in the Collagen Type II (Bovine) Murine Model for Rheumatoid Arthritis by Altering Cytokine Environment
Zimmerman1, Daniel, Talor2, Eyal, Taylor3, Patricia, O'Neill4, Sean, Bendele5, Alison, Rosenthal6, Kenneth
CEL SCI Corporation, Vienna, VA
CEL, Vienna, VA
Northeastern Ohio colleges of Medicine, Rootstown
Washington Biotech, Columbia, MD
BolderBiopath, Bolder, CO
Northeastern Ohio colleges of Medicine, Rootstown, OH
The collagen type II (bovine) (CIA) induced arthritis murine model is often used to evaluate treatments for rheumatoid arthritis (RA). Following initial induction, the disease progresses into a more classical cell and cytokine mediated pathogenesis. We will use this model to evaluate a new therapeutic vaccine for RA
Male (78 week old) DBA/1J mice with CIA induced arthritis were either untreated or treated with the CEL-2000 L.E.A.P.S. experimental therapeutic vaccine or etanercept (Enbrel). CEL-2000 vaccine consists of 2 peptides of human origin, a segment of the beta 2 microglobulin molecule referred to as peptide J and a peptide (254273) from human collagen Type II. Disease was induced by 2 immunizations of bovine type II collagen on day 0 (in CFA) and day 21 (in ICFA). The mice were scored daily for an Arthritic Index (AI) score. Therapy was initiated when the mice (n=8) had a group mean AI score of 3.5 +/- 0.1 and range of 16. CEL-2000 vaccine 33 or 100 nmole was administered on day 0 and 7 of therapy and etanercept 3 mg/kG was administered every other day for the 28 days unless otherwise noted. Mice were evaluated at least 3 times a week for A) footpad swelling and B) AI score. At the termination of the study, tissue sections were evaluated for C) histopathological parameters including 1) inflammation, as evidenced by accumulation of eosinophils, basophils, neutrophils and macrophages, 2) cartilage destruction 3) bone resorption, and 4) pannus membrane formation in the synovial space. D) Sera, collected at the start of therapy and 10 days later, were evaluated for levels of 22 cytokines/chemokines, as measured by the RayBiotech protein array.
By all four parameters there was a statistically significant (p <= 0.05 or better depending on the day of therapy and parameter being considered) benefit of the CEL-2000 vaccine therapy and to a lesser extent for etanercept therapy. CEL-2000 caused an increase in IL-12p70 and IL10 and reduction in disease associated serum levels of TNF-a, IL-17, IL-6, MCP-1 and IL-12p40. A number of cytokine changes were also seen with Enbrel although to a lesser degree
CEL-2000 vaccine administered as a therapy arrested the progression of RA disease and its efficacy was demonstrated by reduction in disease parameters (AI) and in the reduction of serum levels of pro-inflammatory cytokines.
To cite this abstract, please use the following information:
Zimmerman, Daniel, Talor, Eyal, Taylor, Patricia, O'Neill, Sean, Bendele, Alison, Rosenthal, Kenneth; A Therapeutic Vaccine Arrests Disease Progression in the Collagen Type II (Bovine) Murine Model for Rheumatoid Arthritis by Altering Cytokine Environment [abstract]. Arthritis Rheum 2009;60 Suppl 10 :2