From vaccines to nanovaccines: A promising strategy to revolutionize rheumatoid arthritis treatment.

Rheumatoid arthritis (RA) is a joint-related autoimmune disease that is difficult to cure. Most therapeutics act to alleviate the symptoms but not correct the causes of RA. Novel strategies that specifically target the causes are highly needed for RA management. Currently, early interruption of RA is increasingly suggested but the corresponding therapeutics are not available. Vaccines that have shown great success to combat infection, cancer, degenerative diseases, autoimmune diseases, etc. are ideal candidates for a new generation of anti-RA therapeutics to correct the causes and prevent RA or interrupt RA in early phases. Anti-RA vaccines can be divided into two major categories. One is to induce neutralizing antibodies and the other is to induce antigen-specific immune tolerance. The vaccines are inherently linked to nanotechnology because they usually need a biomacromolecule or carrier to provoke sufficient immune responses. In the past decade, designed nanocarriers such as nanoparticles, liposomes, nanoemulsion, etc., have been applied to optimize the vaccines for autoimmune disease treatment. Nanotechnology endows vaccines with a higher biostability, tunable in vivo behavior, better targeting, co-delivery with stimulatory agents, regulatory effects on immune responses, etc. In this review, unmet medical needs for RA treatment and anti-RA vaccinology are first introduced. The development of anti-RA therapies from vaccines to nanovaccines are then reviewed and perspectives on how nanotechnology promotes vaccine development and advancement are finally provided. In addition, challenges for anti-RA vaccine development are summarized and advantages of nanovaccines are analyzed. In conclusion, nanovaccines will be a promising strategy to revolutionize the treatment of RA by correcting the causes in an early phase of RA.