Reverse vaccinology-based design of a universal multiepitope vaccine against chikungunya virus: Phylogenetic and immunoinformatics approaches

Chikungunya virus (CHIKV) infection is a re-emerging arboviral disease in tropical and subtropical regions. In addition to acute febrile syndrome, CHIKV infection may lead to chronic articular manifestations that significantly affect a long-term quality of life. This study aimed to design a universal vaccine candidate covering all circulating genotypes of CHIKV based on conserved multiepitope platform. We employed a large scale phylogenetic and immunoinformatic approach to identify conserved regions of the open reading frames (ORF2) region encoding viral structural proteins. This study ultimately identified 10 high-quality epitopes: 6 MHC-I, 1 MHC-II, and 3 B cell epitopes. The selected epitopes span multiple viral domains, including C, E1, E2, and E3, with high immunogenicity (VaxiJen ≥ 66%), non-toxic, and non-allergenic properties. These selected epitopes were utilized to design multiepitope vaccine constructs (MEV-CHIKV) linked with various linkers in combination with adjuvants (human β-defensin 3) to enhance the immune responses. Structural validation analysis showed high quality and stability of the vaccine construct. Based on molecular docking analysis, the designed vaccine has high binding affinities with the active site of TLR3. In silico immune simulation showed induction of robust adaptive immune responses, characterized by the activation and expansion of B and T cell populations. Codon optimization and rare codon analysis revealed a potentially high expression in bacterial system. Thus, the vaccine cadidate is anticipated to effectively and simultaneously induce robust cellular and humoral immune responses. In addition, it should retain its high protection upon emergence of novel mutations within the CHIKV genome. Since our study is merely in silico-based analysis, further in vitro and in vivo experimental validation to demonstrate the immunogenic properties of the vaccine candidate are still needed.