The induction of immune tolerance is a promising approach for treating autoimmune diseases. Several strategies have been trialled to induce immune tolerance, including the use of antigen-specific peptide vaccines, which have had some success but can trigger unwanted immune responses owing to the use of an adjuvant. The results of a new study suggest that plant viruses could be harnessed to deliver specific peptides without the need for an adjuvant, thereby improving the efficacy of peptide vaccines.

Nanoparticles created from plant virus coat protein subunits can be genetically engineered to express an antigen-specific peptide related to an autoimmune disease. These nanoparticles can then be grown in their natural plant hosts (a technique known as molecular farming) before being collected for use.

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“We started working 20 years ago on molecular farming as an enabling technology to solve the challenges posed by autoimmune diseases, in particular those related to tolerance induction,” says corresponding author Linda Avesani. “In our new paper, we demonstrated for the first time that bio-designed nanomaterials can be used to prevent autoimmune diabetes and to treat autoimmune arthritis.”

Avesani and colleagues created nanoparticles from tomato bushy stunt virus (TBSV) that expressed one of two peptides (pLIP1 or pFADK2), which had previously been identified in a peptide library screen as being immunodominant in patients with seronegative rheumatoid arthritis. Administration of these nanoparticles to mice with collagen-induced arthritis reduced their symptoms (and in the case of pLIP1, abolished them completely) compared with treatment with the same peptide and an adjuvant or with saline, and produced similar or better results to treatment with the glucocorticoid dexamethasone.

In addition, the researchers tested wild-type TBSV on its own, which was also able to reduce the symptoms of arthritis, albeit to a lesser degree than the peptide-engineered nanoparticles, suggesting that TBSV has innate immunomodulatory properties. “These results indicate that the virus structure acts both as a carrier (stabilizing the peptide) and as an adjuvant,” explains Avesani.

Administration of these nanoparticles to mice with collagen-induced arthritis reduced their symptoms

Similar results were also achieved in a model of autoimmune diabetes using a different plant virus. Avesani and colleagues hope to expand their use of this technique to other autoimmune diseases and to develop the nanoparticles for use in humans.