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.
