Revolutionizing Chikungunya Vaccines: mRNA Breakthroughs With Molecular and Immune Simulations

With the ability to cause massive epidemics that have consequences on millions of individuals globally, the Chikungunya virus (CHIKV) emerges as a severe menace. Developing an effective vaccine is urgent as no effective therapeutics are available for such viral infections. Therefore, we designed a novel mRNA vaccine against CHIKV with a combination of highly antigenic and potential MHC-I, MHC-II, and B-cell epitopes from the structural polyprotein. The vaccine demonstrated well-characterized physicochemical properties, indicating its solubility and potential functional stability within the body (GRAVY score of -0.639). Structural analyses of the vaccine revealed a well-stabilized secondary and tertiary structure (Ramachandran score of 82.8% and a Z-score of -4.17). Docking studies of the vaccine with TLR-2 (-1027.7 KJ/mol) and TLR-4 (-1212.4 KJ/mol) exhibited significant affinity with detailed hydrogen bond interactions. Molecular dynamics simulations highlighted distinct conformational dynamics among the vaccine, "vaccine-TLR-2" and "vaccine-TLR-4" complexes. The vaccine's ability to elicit both innate and adaptive immune responses, including the presence of memory B-cells and T-cells, persistent B-cell immunity for a year, and the activation of TH cells leading to the release of IFN-γ and IL-2, has significant implications for its potential effectiveness. The CHIKV vaccine developed in this study shows promise as a potential candidate for future vaccine production against CHIKV, suggesting its suitability for further clinical advancement, including in vitro and in vivo experiments.