Pos0435 peptide-based vaccine targeting il17a attenuates experimental spondyloarthritis inhla-b27 transgenic rats

Background Ankylosing spondylitis (AS) is one of the major diseases in spondyloarthritis (SpA). HLA-B27 is known as a genetic risk factor for AS. Recent lines of evidence suggests that IL-23/IL-17 axis strongly contributes to AS. Objectives This study was to assess the efficacy of IL17A peptide-based vaccine on the SpA manifestations in model rat. Methods HLA-B27/human beta 2 -microglobulin transgenic rats were immunized with heat-inactivated Mycobacterium Tuberculosis (MT) to develop spondylitis and arthritis as an experimental spondyloarthritis model after 3 times immunization with KLH-conjugated IL17A peptide-based vaccine with alum adjuvant. IL17A antibody titer was assessed by ELISA, and arthritis score and joint thickness was monitored twice a week. At 9 weeks, joints of ankle and spine were collected to analyzed by histological analysis and realtime PCR for evaluation of inflammation and bone remodeling. Moreover, heart, liver, and lung were also collected for safety assessment by HE staining. Results IL17A peptide-based vaccine with alum adjuvant successfully induced antibody production, and suppressed arthritis score and joint thickness. X-ray and histological analysis showed that enthesitis, bone destruction, and new bone formation were inhibited by IL-17A vaccine. Moreover, SpA-induced expression of IL17A-related inflammatory- and bone remodeling molecules were down-regulated in the ankle and spine. Finally, IL-17A vaccine had no tissue damage by histological analysis. Conclusion These data showed that peptide-based vaccine targeting IL-17A prevented SpA phenotype in heat-inactivated Mycobacterium Tuberculosis-induced SpA model in HLA-B27/human beta 2 microglobulin transgenic rats. IL17A-peptide based vaccine can be a therapeutic option for SpA treatment. References [1]Nakagami H, Morishita R: Recent Advances in Therapeutic Vaccines to Treat Hypertension. Hypertension 2018, 72(5):1031-1036. [2]Nakagami F, Koriyama H, Nakagami H, Osako MK, Shimamura M, Kyutoku M, Miyake T, Katsuya T, Rakugi H, Morishita R: Decrease in blood pressure and regression of cardiovascular complications by angiotensin II vaccine in mice. PLoS One 2013, 8(3):e60493. Acknowledgements This work was supported by a grant from the Japan Agency for Medical Research and Development 20ek0109312h0003 and 22ek0109565h0002. Disclosure of Interests None Declared.