Department of Health Development and Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
Department of Health Development and Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
RMD Open. 2023 Feb;9(1). doi: 10.1136/rmdopen-2022-002851.
Spondyloarthritis (SpA) is known as series of immune-mediated inflammatory disease of the axial and peripheral joints. Human leucocyte antigen (HLA)-B27 is a genetic risk factor for SpA. Recent evidence suggests that the interleukin -17 (IL17) axis strongly contributes to SpA. This study aimed to assess the efficacy of an IL17A peptide-based vaccine on SpA manifestations in model rats.
HLA-B27/human β-microglobulin (hβM) transgenic rats were immunised with heat-inactivated (MT) to develop spondylitis and arthritis as an experimental SpA model after immunisation with a keyhole limpet hemocyanin-conjugated IL17A peptide-based vaccine with an alum adjuvant three times. The IL17A antibody titre was assessed using ELISA, and arthritis score and joint thickness were monitored two times a week. Enzyme-linked immunospot (ELISpot) assays for IL4- and interferon-γ-secreting splenocytes were conducted to evaluate IL17A-specific T cell activation. We also evaluated the effect of IL17A vaccine in SpA therapeutic model.
The IL17A peptide-based vaccine with alum adjuvant successfully induced antibody production and suppressed the arthritis score and joint thickness. X-ray and histological analyses showed that enthesitis, bone destruction and new bone formation were inhibited by the IL17A vaccine. The ELISpot assay showed that the IL17A peptide-based vaccine did not elicit any IL17A-reactive T cell responses. IL17A vaccine tends to mitigate, but not significant, in SpA treatment model. These data showed that the peptide-based vaccine targeting IL17A alleviated the SpA phenotype in a heat-inactivated MT-induced SpA model in HLA-B27/hβM transgenic rats.
IL17A peptide-based vaccine may be a therapeutic option for SpA treatment.
脊柱关节炎（SpA）是一种已知的免疫介导的中轴和外周关节炎症性疾病系列。人类白细胞抗原（HLA）-B27 是 SpA 的遗传危险因素。最近的证据表明，白细胞介素-17（IL17）轴对 SpA 有很强的贡献。本研究旨在评估基于 IL17A 肽的疫苗对模型大鼠 SpA 表现的疗效。
用热灭活（MT）免疫 HLA-B27/人β-微球蛋白（hβM）转基因大鼠，用钥孔血蓝蛋白（KLH）偶联的基于 IL17A 肽的疫苗和明矾佐剂免疫三次，建立脊柱关节炎和关节炎作为实验性 SpA 模型。使用 ELISA 评估 IL17A 抗体滴度，每周监测两次关节炎评分和关节厚度。进行酶联免疫斑点（ELISpot）分析以评估分泌 IL4 和干扰素-γ的脾细胞，以评估 IL17A 特异性 T 细胞的激活。我们还评估了 IL17A 疫苗在 SpA 治疗模型中的作用。
KLH 偶联的基于 IL17A 肽的疫苗加明矾佐剂成功诱导了抗体产生，并抑制了关节炎评分和关节厚度。X 射线和组织学分析表明，IL17A 疫苗抑制附着点炎、骨破坏和新骨形成。ELISpot 分析表明，基于 IL17A 肽的疫苗不会引起任何 IL17A 反应性 T 细胞反应。IL17A 疫苗在 SpA 治疗模型中倾向于减轻，但不显著。这些数据表明，针对 IL17A 的肽疫苗减轻了 HLA-B27/hβM 转基因大鼠中热灭活 MT 诱导的 SpA 模型中的 SpA 表型。
基于 IL17A 肽的疫苗可能是治疗 SpA 的一种选择。
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