Are we going to have vaccine for rheumatoid arthritis?

There are no preventive measures for rheumatoid arthritis (RA) and for the past few decades, researchers have been exploring the possibility of having a vaccine.

CEL-SCI Corporation, a biotechnology company, in collaboration with scientists at Rush university medical centre, USA, has developed a T cell-targeting vaccine called CEL-4000. In animal models, it was able to down-modulate inflammatory response by decreasing Th1, Th17 IFNγ, and IL17A cytokines and increasing IL4 and IL10 anti-inflammatory cytokines production. According to the researchers, CEL-4000 is cost-effective and easy to manufacture when compared to biologics used in RA.

In Australia, an RA vaccine called Rheumavax was assessed on 18 RA patients in a clinical trial led by Dr. Ranjeny Thomas. The patients’ own dendritic cells were tolerized to anti-CCP and injected back to the subjects. A nanoparticle therapy named DEN-181 was developed by Dr. Phillip Vecchio and Dr. Amee Sonigra at TRI’s Clinical Research Facility in the Princess Alexandra Hospital (PAH) campus. A clinical trial involving 17 patients has found the DEN-181 was safe and able to modulate antigen-specific T cells.1

Yun-Rak Choi and co-researchers at Washington University School of Medicine in St. Louis have edited induced pluripotent stem cells (iPSCs) to release the anti-cytokine biologic drug in response to RA inflammation using CRISPR-Cas9 genome editing. They genetically reprogrammed the stem cells gene to release biological drugs to reduce inflammation by binding to interleukin-1 (IL-1).

The implantation of genetically engineered cartilage cells under mice skin allowed the cells persistence for a longer period and their release upon episodes of inflammation.

Dr. Ritu Chakravarti and co-researchers at the University of Toledo have developed vaccine treatment based on 14-3-3 zeta protein. The researchers initially tried to knock off the gene in a mouse model with arthritis, as 14-3-3 zeta protein plays a key role in the onset of RA.

To their surprise, the results were contrasted, as it hastened the progression of the disease. They further developed a new protein-based vaccine based on stimulation of 14-3-3 zeta protein, which was able to prevent the disease development in animal models. The study was published in the journal Proceedings of the National Academy of Sciences.

Although the studies are promising, it may take a long way to translate these results from bench to bedside. The development of an RA vaccine will revolutionize the treatment paradigm in rheumatology.