Design of a Multi‐Epitope Vaccine Targeting α‐Synuclein for Parkinson's Disease Using Immunoinformatics Tools

ABSTRACT Parkinson's disease (PD) is one of the neurodegenerative diseases that most affects the population, especially those over 65 years old. It is characterized by motor difficulties such as resting tremors, muscle stiffness, slow movements, and lack of balance, significantly impacting the quality of life of these individuals. Experimental studies suggest that the protein α‐synuclein (α‐syn) causes PD by leading to the death of dopaminergic neurons, contributing to the worsening severity of this disease's symptoms. Considering the relevance of this protein in the development of PD, it could be an ideal target for the development of therapeutic vaccines for this condition. The aim of this study was to design a multi‐epitope vaccine using peptide constructs derived from α‐syn and bromelain as an adjuvant, based on immunoinformatics tools. A total of five B‐cell epitope sequences and 15 TCD4+ cell (MHC‐II) epitope sequences restricted to the most prevalent alleles were selected. The chosen epitopes were antigenic, non‐allergenic, and non‐toxic and were linked using AAY, KK, GPGPG, and EAAAK linkers to create vaccine constructs with enhanced immunogenicity, stability, and flexibility. The tertiary structures, model refinement of the initial structure, Ramachandran plots, and ProsaWeb predictions were assessed. Molecular docking and molecular dynamics simulation studies showed efficient binding of Vaccine 2 with the TLR2 and TLR4 receptors. In general, in silico approaches have demonstrated the potential of peptide‐based vaccine constructs, designed from immunodominant epitopes of α‐syn and bromelain, for the development of a multiepitope therapeutic vaccine against PD.