Multiepitope subunit vaccine against Colorado tick fever virus by using reverse vaccinology approach

Abstract

Despite being a medically significant tick-borne virus, little research has been done on the Colorado tick fever virus. This virus is a member of the Spinareoviridae family and is mainly spread in the western parts of the United States and southwest Canada. It is classified as a Coltivirus. The main vector of the virus, Dermacentor andersoni, a wood tick found in the Rocky Mountains, determines patterns of viral spread. Furthermore, no effective antiviral treatment or vaccine has yet been created to guard against viral infections. An alternate method of preventing viral infections is vaccination. To stop a potential pandemic in the future, a thermodynamically stable and economical vaccination should be discovered. The goal of this study was to develop a potential vaccine against the Colorado tick fever virus. We seek to identify epitopes within two critical proteins, the Colorado tick fever virus's structural protein VP9 and the RNA-directed RNA polymerase VP1, to predict the precise locations that B and T cells will recognize by using a variety of reverse vaccinology and Computational techniques. Through modelling, the epitopes were deliberately engineered to connect with their corresponding HLA molecules, serving as the foundation for a multi-epitope subunit vaccination. This meticulously crafted vaccination candidate was created by joining B and T cell epitopes that had been extensively examined and linked with the appropriate linkers. Numerous physiological characteristics, including molecular weight, instability index, and aliphatic index, were assessed for the vaccine model, it was 3D modelled to dock with TLR-4. Previous research suggested that adding human beta-defensin as an adjuvant to the vaccine sequence at the N-terminus might improve immunogenicity. Additionally, the C-IMMSIM server ran immunological simulations to confirm the final vaccine design. The immunological simulation analysis anticipated a natural immune response. E. coli was used as the host for in-silico cloning, and the 0.96 CAI value obtained indicates that the vaccine construct will express itself to its fullest extent in the E. coli host. The binding mode of vaccine construct has been investigated via molecular docking approach against TLR4 human receptor protein. Vaccine created in this study shown efficacious and immunogenic response during immune simulation. Furthermore, this was more accurately validated through molecular dynamic simulations where the receptor molecule strongly bonds to the active residues of the epitope during 200 ns simulation time intervals. No certain changes were inferred among both receptor molecules and epitope during this time interval and remains static. Thus, these investigations result in determining the effectiveness in treating infections caused by the Colorado tick fever virus, which will allow experimentalists for its further validation to tackle this disease.