Peptide-based vaccine targeting IL17A attenuates experimental spondyloarthritis in HLA-B27 transgenic rats

针对 IL17A 的肽基疫苗可减轻 HLA-B27 转基因大鼠的实验性脊柱关节炎

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作者:Hiroki Hayashi, Jiao Sun, Yuka Yanagida, Shota Yoshida, Satoshi Baba, Akiko Tenma, Masayoshi Toyoura, Sotaro Kawabata, Takako Ehara, Ryoko Asaki, Makoto Sakaguchi, Hideki Tomioka, Munehisa Shimamura, Ryuichi Morishita, Hiromi Rakugi, Tetsuya Tomita, Hironori Nakagami

Conclusions

IL17A peptide-based vaccine may be a therapeutic option for SpA treatment.

Methods

HLA-B27/human β2-microglobulin (hβ2M) transgenic rats were immunised with heat-inactivated Mycobacterium tuberculosis (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.

Results

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/hβ2M transgenic rats. Conclusions: IL17A peptide-based vaccine may be a therapeutic option for SpA treatment.

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