Altered Peptide Ligand (APL) Therapeutic Vaccine against Autoimmune Disease: Rheumatoid Arthritis

Abstract

Rheumatoid Arthritis (RA) is a prevalent autoimmune disease, affecting millions worldwide. Its treatment is often costly, placing a significant economic burden on patients and healthcare systems. Current therapies primarily rely on immunosuppression, which can have drawbacks, such as increased susceptibility to infections and long-term medication dependency. The development of targeted APL vaccines represents a promising avenue for more effective and safer RA management, offering hope for improved patient outcomes and reduced treatment costs in the future. In this research, an Altered Peptide Ligand (APL) therapeutic vaccine against Rheumatoid Arthritis (RA) was designed through in silico methods. The Vimentin protein sequence, sourced from NCBI, served as the starting point. A specific B cell epitope, "STRTYSLGSALRPSTSRSLY," which exhibited strong binding with both HLADRB1 and HLADRB4 receptors, was the focus. However, it demonstrated high immunogenicity and IFN-γ production, coupled with reduced IL10 and IL4 levels. To enhance its regulatory response while reducing inflammation, a double substitution was performed. At positions 1 and 3, S was replaced by E, and R was substituted with E, respectively. Remarkably, these alterations did not compromise binding to HLADRB1. Furthermore, the peptide was linked to Alpha-Melanocyte Stimulating Hormone through an EAAAK linker. The resultant sequence, "SYSMEHFRWGKPVEAAAKETETYSLGSALRPSTSRSLY," exhibited reduced IFN-γ production and increased IL10 and IL4 levels. This innovative peptide is proposed as a potential APL vaccine candidate against RA, underscoring the efficacy of in silico methodologies in therapeutic vaccine design.