Peptide-based vaccine targeting IL17A attenuates experimental spondyloarthritis in HLA-B27 transgenic rats
Objectives 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...
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BMJ Publishing Group
2023-02-01
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| Series: | RMD Open |
| Online Access: | https://rmdopen.bmj.com/content/9/1/e002851.full |
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| author | Tetsuya Tomita Hiromi Rakugi Hiroki Hayashi Ryuichi Morishita Jiao Sun Yuka Yanagida Shota Yoshida Satoshi Baba Akiko Tenma Masayoshi Toyoura Sotaro Kawabata Takako Ehara Ryoko Asaki Makoto Sakaguchi Hideki Tomioka Munehisa Shimamura Hironori Nakagami |
| author_facet | Tetsuya Tomita Hiromi Rakugi Hiroki Hayashi Ryuichi Morishita Jiao Sun Yuka Yanagida Shota Yoshida Satoshi Baba Akiko Tenma Masayoshi Toyoura Sotaro Kawabata Takako Ehara Ryoko Asaki Makoto Sakaguchi Hideki Tomioka Munehisa Shimamura Hironori Nakagami |
| author_sort | Tetsuya Tomita |
| collection | DOAJ |
| description | Objectives 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.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. |
| format | Article |
| id | doaj-art-f1e439622aa643a9ab0805098beb61be |
| institution | Kabale University |
| issn | 2056-5933 |
| language | English |
| publishDate | 2023-02-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | RMD Open |
| spelling | doaj-art-f1e439622aa643a9ab0805098beb61be2025-02-03T08:10:10ZengBMJ Publishing GroupRMD Open2056-59332023-02-019110.1136/rmdopen-2022-002851Peptide-based vaccine targeting IL17A attenuates experimental spondyloarthritis in HLA-B27 transgenic ratsTetsuya Tomita0Hiromi Rakugi1Hiroki Hayashi2Ryuichi Morishita3Jiao Sun4Yuka Yanagida5Shota Yoshida6Satoshi Baba7Akiko Tenma8Masayoshi Toyoura9Sotaro Kawabata10Takako Ehara11Ryoko Asaki12Makoto Sakaguchi13Hideki Tomioka14Munehisa Shimamura15Hironori Nakagami1620 Graduate School of Health Science, Morinomiya University of Medical Sciences, Osaka City, Osaka, JapanDepartment of Geriatric and General Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan1Chugai Pharmaceutical Co. Ltd., Yokohama, Kanagawa, JapanDepartment of Clinical Gene Therapy, Osaka University Graduate School of Medicine, Suita, Osaka, JapanDepartment of Health Development and Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, JapanDepartment of Health Development and Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, JapanDepartment of Health Development and Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan6 Department of Diagnostic Pathology, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, JapanFunPep.Co, Suita, Osaka, JapanFunPep.Co, Suita, Osaka, JapanFunPep.Co, Suita, Osaka, JapanFunPep.Co, Suita, Osaka, JapanFunPep.Co, Suita, Osaka, JapanFunPep.Co, Suita, Osaka, JapanFunPep.Co, Suita, Osaka, JapanDepartment of Health Development and Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, JapanDepartment of Health Development and Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, JapanObjectives 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.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.https://rmdopen.bmj.com/content/9/1/e002851.full |
| spellingShingle | Tetsuya Tomita Hiromi Rakugi Hiroki Hayashi Ryuichi Morishita Jiao Sun Yuka Yanagida Shota Yoshida Satoshi Baba Akiko Tenma Masayoshi Toyoura Sotaro Kawabata Takako Ehara Ryoko Asaki Makoto Sakaguchi Hideki Tomioka Munehisa Shimamura Hironori Nakagami Peptide-based vaccine targeting IL17A attenuates experimental spondyloarthritis in HLA-B27 transgenic rats RMD Open |
| title | Peptide-based vaccine targeting IL17A attenuates experimental spondyloarthritis in HLA-B27 transgenic rats |
| title_full | Peptide-based vaccine targeting IL17A attenuates experimental spondyloarthritis in HLA-B27 transgenic rats |
| title_fullStr | Peptide-based vaccine targeting IL17A attenuates experimental spondyloarthritis in HLA-B27 transgenic rats |
| title_full_unstemmed | Peptide-based vaccine targeting IL17A attenuates experimental spondyloarthritis in HLA-B27 transgenic rats |
| title_short | Peptide-based vaccine targeting IL17A attenuates experimental spondyloarthritis in HLA-B27 transgenic rats |
| title_sort | peptide based vaccine targeting il17a attenuates experimental spondyloarthritis in hla b27 transgenic rats |
| url | https://rmdopen.bmj.com/content/9/1/e002851.full |
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