Designing a multi-epitope vaccine against yellow fever virus using immunoinformatics approaches

Objectives Yellow fever virus (YFV) is a mosquito-borne pathogen causing severe hemorrhagic fever in tropical and subtropical regions. This study aimed to design and evaluated a multi-epitope subunit vaccine against yellow fever virus using immunoinformatics and computational approaches. Methods The yellow fever virus envelope glycoprotein was selected as the target antigen. Antigenic, non-allergenic, and non-toxic B-cell, MHC-I, and MHC-II epitopes were predicted and assembled into a vaccine construct using linkers and β-defensin-3 as an adjuvant. Structural modeling and validation were performed using AlphaFold3 and quality assessment tools. Molecular docking with TLR2 and TLR8 was conducted using ClusPro, followed by molecular dynamics simulations to assess structural stability. Disulfide engineering was applied to enhance rigidity, immune simulation was performed to predict host immune responses, and in silico cloning was carried out using the pBR322 vector. Results Six conserved epitopes with strong antigenic potential were identified. The vaccine construct showed favorable docking interactions with TLR2 and TLR8, yielding ClusPro weighted interaction scores of −1105.52 and −1152.9, respectively. Molecular dynamics simulations revealed structural stability, supported by stable RMSD and compact radius of gyration profiles. Immune simulation indicated robust humoral and cellular immune responses. Conclusions The designed multi-epitope vaccine showed promising immunogenic and structural properties, supporting its potential as a potential vaccine candidate against yellow fever virus. However, experimental validation through in vitro and in vivo studies is required.