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Updated: Jul 13, 2025
An Adoptive Transfer Model of Rheumatoid Arthritis in Mice
Published on: June 6, 2025
mRNA vaccine against fibroblast activation protein ameliorates murine models of inflammatory arthritis
Xiaowei Zhang1, Antony Jozic2,3,4, Pingfang Song1
1Division of Arthritis and Rheumatic Diseases, Oregon Health & Science University, VA Portland Health Care System, Portland, Oregon 97239, USA.
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.
Insights
A novel vaccine targeting fibroblast activation protein (FAP) suppressed inflammatory arthritis in mouse models. This fibroblast activation protein mRNA-lipid nanoparticle vaccine shows promise for rheumatoid arthritis (RA) therapy.
Area of Science:
- Immunology
- Rheumatology
- Molecular Therapy
Background:
- Synovial fibroblasts in rheumatoid arthritis (RA) drive synovitis and joint destruction, representing key therapeutic targets.
- Fibroblast activation protein (FAP) is highly and specifically expressed on RA synovial fibroblasts.
- Targeting FAP offers a potential strategy to modulate fibroblast activity in inflammatory arthritis.
Purpose of the Study:
- To evaluate the therapeutic potential of a fibroblast activation protein (FAP) targeting vaccine in experimental arthritis models.
- To assess if FAP can serve as a molecular target for modulating synovial fibroblasts in arthritis therapy.
Main Methods:
- Messenger RNA (mRNA) encoding consensus FAP (cFAP) was encapsulated in lipid nanoparticles (LNPs) to create a vaccine.
- The cFAP mRNA-LNP vaccine was administered intramuscularly before inducing collagen-induced arthritis (CIA) and collagen antibody-induced arthritis (CAIA) in mice.
- Arthritis development was monitored clinically and histologically.
Main Results:
- The cFAP mRNA-LNP vaccine successfully induced an immune response against both consensus FAP (cFAP) and mouse FAP (mFAP).
- In the CIA model, the vaccine prevented arthritis onset in 40% of mice and significantly reduced overall disease severity.
- In the CAIA model, while not preventing onset, the vaccine significantly decreased arthritis severity.
Conclusions:
- The cFAP mRNA-LNP vaccine effectively elicits an immune response targeting FAP.
- This FAP-targeting vaccine demonstrates efficacy in suppressing inflammatory arthritis in preclinical models, suggesting therapeutic potential for RA.
