Dataset Information

MRNA vaccine against fibroblast activation protein ameliorates murine models of inflammatory arthritis.

ABSTRACT:

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.

SUBMITTER: Zhang X

PROVIDER: S-EPMC10561064 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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Publications

mRNA vaccine against fibroblast activation protein ameliorates murine models of inflammatory arthritis.

Zhang Xiaowei X Jozic Antony A Song Pingfang P Xu Qiang Q Shi Xiaofei X Wang Hong H Bishop Lindsey L Struthers Hillary M HM Rutledge John J Chen Shuang S Xu Fei F Hancock Meaghan H MH Zhu Daocheng D Sahay Gaurav G Chu Cong-Qiu CQ

Rheumatology and immunology research 20230601 2

<h4>Objective</h4>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.<h4>Methods</h4>mRNA encoding cons ...[more]

PMID: 37818347

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