Designing a multi-epitope subunit vaccine against chikungunya virus using immunoinformatics and molecular simulation approaches

Chikungunya is a mosquito-borne viral illness that is responsible for increased rates of infection and major public health consequences, but no approved vaccine is available yet. This research employed an integrated approach of immunoinformatics and structural vaccinology to develop a promising multi-epitope subunit vaccine candidate. This study focused on the conserved structural polyprotein (NP_690589) for the purpose of epitope predictions. After strict filtering for high antigenicity, safety, and excellent conservation (> 90%), 9 CTL epitopes, 8 HTL epitopes, and 5 B-cell epitopes were selected. The ultimate vaccine formulation, associated with beta-defensin-3 as an adjuvant, demonstrated favorable physicochemical characteristics, robust antigenicity (score 0.7317), and an anticipated global population coverage of 91.79%. Molecular docking revealed very stable binding to human TLR4 and TLR2. TLR4 was further confirmed by 100 ns MD simulation. Thereafter, an immune simulation study revealed the potentiality of the vaccine to augment both innate and adaptive immune responses. Codon optimization was done for efficient expression in E. coli. The mRNA of the proposed vaccine exhibited stability in in vivo conditions. This in silico-designed vaccine candidate suggests it is highly immunogenic, physically stable, and widely protective. It is a strong candidate that now needs experimental validation to move toward preclinical testing.