Xiaowei Zhang, Antony Jozic, Pingfang Song, Qiang Xu, Xiaofei Shi, Hong Wang, Lindsey Bishop, Hillary M Struthers, John Rutledge, Shuang Chen, Fei Xu, Meaghan H Hancock, Daocheng Zhu, Gaurav Sahay, Cong-Qiu Chu
{"title":"针对成纤维细胞活化蛋白的信使核糖核酸疫苗可改善炎症性关节炎小鼠模型。","authors":"Xiaowei Zhang, Antony Jozic, Pingfang Song, Qiang Xu, Xiaofei Shi, Hong Wang, Lindsey Bishop, Hillary M Struthers, John Rutledge, Shuang Chen, Fei Xu, Meaghan H Hancock, Daocheng Zhu, Gaurav Sahay, Cong-Qiu Chu","doi":"10.2478/rir-2023-0013","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>Synovial fibroblasts in patients with rheumatoid arthritis (RA) contribute substantially to the perpetuation of synovitis and invasion to cartilage and bone, and are potential therapeutic targets. Fibroblast activation protein (FAP) is highly expressed by RA synovial fibroblasts and the expression is relatively specific. We tested whether FAP can serve as a molecular target to modulate synovial fibroblasts for therapy in experimental arthritis.</p><p><strong>Methods: </strong>mRNA encoding consensus FAP (cFAP) was encapsulated in lipid nanoparticles (LNP) and was injected intramuscularly as vaccine prior to induction of collagen-induced arthritis (CIA) and collagen antibody induced arthritis (CAIA) in mice. Development of CIA and CAIA was assessed clinically and by histology.</p><p><strong>Results: </strong>cFAP mRNA-LNP vaccine provoked immune response to cFAP and mouse FAP (mFAP); prevented onset of CIA in 40% of mice and significantly reduced the severity of arthritis. In CAIA, cFAP mRNA-LNP did not prevent onset of arthritis but significantly reduced the severity of arthritis.</p><p><strong>Conclusion: </strong>cFAP mRNA-LNP vaccine was able to provoke immune response to mFAP and suppress inflammatory arthritis.</p>","PeriodicalId":74736,"journal":{"name":"Rheumatology and immunology research","volume":"4 2","pages":"90-97"},"PeriodicalIF":0.0000,"publicationDate":"2023-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10561064/pdf/","citationCount":"0","resultStr":"{\"title\":\"mRNA vaccine against fibroblast activation protein ameliorates murine models of inflammatory arthritis.\",\"authors\":\"Xiaowei Zhang, Antony Jozic, Pingfang Song, Qiang Xu, Xiaofei Shi, Hong Wang, Lindsey Bishop, Hillary M Struthers, John Rutledge, Shuang Chen, Fei Xu, Meaghan H Hancock, Daocheng Zhu, Gaurav Sahay, Cong-Qiu Chu\",\"doi\":\"10.2478/rir-2023-0013\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>Synovial fibroblasts in patients with rheumatoid arthritis (RA) contribute substantially to the perpetuation of synovitis and invasion to cartilage and bone, and are potential therapeutic targets. Fibroblast activation protein (FAP) is highly expressed by RA synovial fibroblasts and the expression is relatively specific. We tested whether FAP can serve as a molecular target to modulate synovial fibroblasts for therapy in experimental arthritis.</p><p><strong>Methods: </strong>mRNA encoding consensus FAP (cFAP) was encapsulated in lipid nanoparticles (LNP) and was injected intramuscularly as vaccine prior to induction of collagen-induced arthritis (CIA) and collagen antibody induced arthritis (CAIA) in mice. Development of CIA and CAIA was assessed clinically and by histology.</p><p><strong>Results: </strong>cFAP mRNA-LNP vaccine provoked immune response to cFAP and mouse FAP (mFAP); prevented onset of CIA in 40% of mice and significantly reduced the severity of arthritis. In CAIA, cFAP mRNA-LNP did not prevent onset of arthritis but significantly reduced the severity of arthritis.</p><p><strong>Conclusion: </strong>cFAP mRNA-LNP vaccine was able to provoke immune response to mFAP and suppress inflammatory arthritis.</p>\",\"PeriodicalId\":74736,\"journal\":{\"name\":\"Rheumatology and immunology research\",\"volume\":\"4 2\",\"pages\":\"90-97\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2023-07-22\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10561064/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Rheumatology and immunology research\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.2478/rir-2023-0013\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2023/6/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Rheumatology and immunology research","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.2478/rir-2023-0013","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/6/1 0:00:00","PubModel":"eCollection","JCR":"","JCRName":"","Score":null,"Total":0}
mRNA vaccine against fibroblast activation protein ameliorates murine models of inflammatory arthritis.
Objective: Synovial fibroblasts in patients with rheumatoid arthritis (RA) contribute substantially to the perpetuation of synovitis and invasion to cartilage and bone, and are potential therapeutic targets. Fibroblast activation protein (FAP) is highly expressed by RA synovial fibroblasts and the expression is relatively specific. We tested whether FAP can serve as a molecular target to modulate synovial fibroblasts for therapy in experimental arthritis.
Methods: mRNA encoding consensus FAP (cFAP) was encapsulated in lipid nanoparticles (LNP) and was injected intramuscularly as vaccine prior to induction of collagen-induced arthritis (CIA) and collagen antibody induced arthritis (CAIA) in mice. Development of CIA and CAIA was assessed clinically and by histology.
Results: cFAP mRNA-LNP vaccine provoked immune response to cFAP and mouse FAP (mFAP); prevented onset of CIA in 40% of mice and significantly reduced the severity of arthritis. In CAIA, cFAP mRNA-LNP did not prevent onset of arthritis but significantly reduced the severity of arthritis.
Conclusion: cFAP mRNA-LNP vaccine was able to provoke immune response to mFAP and suppress inflammatory arthritis.
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