Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement
The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.
Active Immunization Against IL-23 p19 Improves Collagen-Induced-Arthritis
Duvallet1, Emilie, Ratsimandresy2, Rojo, Assier1, Eric, Delavallee1, Laure, Bessis1, N., Zagury2, Jean-François, Boissier3, Marie-Christophe
IL-23 is a pro-inflammatory cytokine known to be essential for the differentiation of the Th17 lymphocytes, a subtype of T lymphocytes implied in autoimmunity. Its subunit, IL-23 p19, is specific of this cytokine. We had previously demonstrated for IL-1beta and TNF-alpha, that active immunization against these cytokines could be protective in animal models of arthritis. The aim of this study was to evaluate the effect of two vaccines targeting the IL-23 p19 subunit, IL23-K1 and IL23-K2, on collagen-induced-arthritis (CIA).
Using bioinformatics, we defined two peptides in IL-23 p19. Each peptide was coupled with keyhole limpet hemocyanin (KLH). Anti-murine IL-23 immunization was performed by injecting intra-muscularly IL23-K1 or IL23-K2 formulated in incomplete Freund adjuvant (IFA), four times (D0, 7, 28, 49) in DBA/1 mice. Control groups received KLH or PBS at the same dates. CIA was 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. Anti-IL-23 and anti-KLH antibody levels were assessed by ELISA. Pro and anti-inflammatory cytokines were quantified by qRT-PCR on the spleen and the synovium.
The clinical scores show that mice treated with either IL23-K1 or IL23-K2 develop less arthritis than the negative controls (p<0.05). Mice vaccinated by IL23-K1 produced more anti-IL23 antibodies than the one vaccinated by KLH (p<0.001). mRNA quantification showed that the IL23-K1 vaccination led to an increase of IL-10 in the spleen (p<0.05 vs KLH), without any effect on IL-17 level. Histology examination showed that IL23-K1 permitted a strong decrease of the joint destruction and inflammation (p<0.01 vs KLH and p<0.001 vs PBS).
These data show that targeting IL-23 p19 using a vaccination strategy may be efficient in CIA.
To cite this abstract, please use the following information:
Duvallet, Emilie, Ratsimandresy, Rojo, Assier, Eric, Delavallee, Laure, Bessis, N., Zagury, Jean-François, et al; Active Immunization Against IL-23 p19 Improves Collagen-Induced-Arthritis [abstract]. Arthritis Rheum 2009;60 Suppl 10 :4