In silico design of a citrullinated protein-based multi-epitope vaccine for rheumatoid arthritis using...

Rheumatoid arthritis (RA) is a chronic autoimmune disorder marked by synovial inflammation and joint deformity. Anti-citrullinated protein antibodies is one of the key biomarkers for RA, produced against citrullinated peptides and contribute to inflammation by forming immune complexes. While current RA treatments may help in managing the symptoms, they may compromise the immune system by increasing vulnerability to infections. In this study, an immunoinformatics approach was used to design a multi-epitope vaccine targeting citrullinated peptides associated with RA. Citrullinated peptides were sourced from the IEDB database and screened for high antigenicity, non-allergenicity and non-toxicity. Vaccine constructs V1, V2, V3 were designed using these peptides with adjuvants 50S ribosomal protein L7/L12 and HbhA protein from Mycobacterium tuberculosis and Human β Defensin-3. 3D models of the vaccine constructs were generated, validated and docked with TLR-4, TLR-2 and HLA-DRB1*04:01 using ClusPro. The vaccine construct V2 displayed lowest binding energy and showed potential results along with stability through immune and MD simulations. The V2 vaccine construct has to be evaluated further through in vitro and in vivo studies. The future experimental validation of our vaccine construct V2 may enhance treatment outcomes and advance the field of vaccine development for RA.