Major breakthrough: scientists have created the world’s first vaccine against rheumatoid arthritis

The protein-based vaccine shows significant promise in preventing rheumatoid arthritis and improving bone quality, suggesting long-term benefits after immunization. (CREDIT: Creative Commons)

Researchers at the University of Toledo have developed an experimental vaccine that shows significant promise in preventing rheumatoid arthritis, a painful autoimmune disease that currently has no cure.

The results, detailed in an article published in Proceedings of the National Academy of Sciences, represent a major breakthrough in the study of rheumatoid arthritis and autoimmune diseases in general.

Rheumatoid arthritis, one of the most common autoimmune diseases, occurs when the body’s immune system attacks and destroys healthy tissue, especially the lining of the joints of the hands, wrists, ankles, and knees.

By some estimates, rheumatoid arthritis affects up to 1% of the world’s population.

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“Despite its high prevalence, there is no cure and we don’t quite know what causes it. This is true for almost all autoimmune diseases, which makes them so difficult to treat or prevent,” said Dr. Ritu Chakravarty, assistant professor at UToledo College of Medicine and Life Sciences and lead author of the paper. “If we can successfully deliver this vaccine to the clinic, it will be revolutionary.”

Chakravarty has been studying a protein called 14-3-3 zeta for many years and its role in immune pathologies, including aortic aneurysms and interleukin-17, a cytokine associated with autoimmune disease. Building on their previous work, the research team focused on protein as a potential trigger for rheumatoid arthritis.

Instead, they found the opposite.

Instead of preventing rheumatoid arthritis, the researchers found that deleting the protein with gene-editing technology caused severe early arthritis in animal models.

Dr. Ritu Chakravarty, Associate Professor, College of Medicine and Life Sciences, University of Toledo. (CREDIT: Daniel Miller | University of Toledo)

Working on a new theory that the 14-3-3 zeta protein protects against rheumatoid arthritis, the team developed a protein vaccine using purified 14-3-3 zeta protein grown in a bacterial cell.

They found that the vaccine elicited a strong and immediate but lasting response from the body’s innate immune system, providing protection against disease.

Knockout rats exhibit severe and early AI. (A) WT (n=8) and KO (n=8) animals were subjected to PIA. The experiment was repeated at least three times. Representative weight gain and IA score during PIA are shown. (B) Representative images showing the inflamed joint in WT animals compared to knockout are shown. (C) 3D CT reconstruction of the ankle and knee joints is shown. (Scale: 1 mm.) (D) Hematoxylin and eosin (H&E) staining of ankles harvested from WT or 14-3-3ζ KO rats were compared for bone damage and immune cell infiltration. (Scale: 200 µm.) (E) 14-3-3ζ antibody levels in synovial fluid were measured in wild-type and knockout animals by ELISA. (F and G) Plasma profile of IL-17A and IL-6 measured in WT and KO animals using ELISA. (CREDIT: University of Toledo)

“To our great surprise, rheumatoid arthritis completely disappeared in the animals that received the vaccine,” Chakravarty said. “Sometimes there is no better way than a happy accident. We accidentally hit the wrong result, but it turned out to be the best result. Such scientific discoveries are very important in this field.”

In addition to suppressing the development of arthritis, the vaccine also significantly improved bone quality, a finding that suggests there should be long-term benefits after immunization.

Immunization with 14-3-3ζ suppresses IA in WT LEW rats. (A) 8-week-old WT LEW rats were subjected to PIA followed by injection of IFA alone or mixed with 14-3-3ζ protein as shown in Fig. 3A. Animals were monitored for body weight and arthritis scores (n = 4). The experiment was repeated at least three times; a representative experiment is shown. (B) Representative images of inflamed joints are shown. (C and D) Plasma (C) and synovial fluid (D) 14-3-3ζ antibody levels were measured by standardized ELISA. (E) Plasma levels of IL-17A in IFA-treated animals compared to IFA+14-3-3ζ-treated animals were measured by ELISA. (F) H&E staining shows the effect of 14-3-3ζ immunization on immune cell infiltration in the ankle joint. (Scale: 500 µm.) An enlarged image of the insert is shown on the right. (Scale bar: 200 µm.) (G) 3D reconstructions of IFA and IFA+14-3-3ζ-treated animals show the effect of 14-3-3ζ immunization on trabecular bone and cortical bone thickness. Scale bar: 1 mm. **P<0.005 and ****P<0.0001. (CREDIT: University of Toledo)

Currently, rheumatoid arthritis is treated primarily with corticosteroids, large-scale immunosuppressants, or newer, more targeted biologics that target a specific inflammatory process.

While these therapies can relieve pain and slow disease progression, they can also make patients more vulnerable to infections and, in the case of biologics, can be expensive.

14-3-3ζ promotes collagen synthesis. (A and B) Tibia (A) and trabecular bones (B) from WT and 14-3-3ζ KO-untreated, IFA- and IFA + 14-3-3ζ-treated arthritic animals were stained for collagen with Mason’s trichrome. (Scale: 500 µm and 50 µm for A and B, respectively.) (C) Primary rat mesenchymal cells were treated with various amounts of purified recombinant protein His-14-3-3ζ for 14 days, and the effect on collagen1 gene induction was measured by RT -qPCR. (CREDIT: University of Toledo)

“In many years, we have not made any really big discoveries in the field of treatment or prevention of rheumatoid arthritis,” said Chakravarty. “Our approach is completely different. This is a vaccine-driven strategy based on a new target that we hope can treat or prevent rheumatoid arthritis. The potential here is huge.”

The researchers have applied for a patent on their discovery and are seeking partners from the pharmaceutical industry to support safety and toxicity studies in the hope of conducting preclinical trials.

To learn more about science and technology, visit our New Discoveries section at The bright side of the news.

Note. Materials provided above by the University of Toledo. Content can be edited for style and length.

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