Computational Design of a Multi-epitope Vaccine Against : An Immunoinformatics Approach.

Unlabelled: Blackleg is an infectious disease of animals that is commonly caused by and characterized by localized muscle necrosis. In this study, proteome-mining and immunoinformatics approaches were applied to identify novel antigenic proteins and to construct a multi-epitope vaccine against . . All proteins of . strains were retrieved from the NCBI Microbial Genome Database containing both genomic and proteomic data of prokaryotes. The proteins were analyzed to exclude non-redundant sequences and to determine antigenic, virulent, and non-allergenic vaccine candidates through several online tools, resulting in seven protein candidates. Cytotoxic T and B cell epitopes of these proteins were evaluated through the tools present in the immune epitope database and the prioritized antigenic epitopes were then conjugated via appropriate linkers to construct the vaccine candidate. After the evaluation of physicochemical properties of the construct, the tertiary structure was modeled and refined through trRosetta and GalaxyRefine, respectively. The quality of the 3D structure was validated by ERRAT score, z-score, and Ramachandran plot and the construct was then docked with bovine Toll-like receptor 4 (TLR 4) using ClusPro. The docked complex was subjected to Molecular Mechanics/Generalized Born Surface Area in the HawkDock server and normal mode analysis in the iMODS simulation suite to assess the binding energy and stability of the complex, respectively. Overall, the vaccine construct was found stable and energetically feasible for bovine TLR 4 binding. Therefore, it can be used as a multi-epitope vaccine construct in clostridial vaccines to control the blackleg disease.

Supplementary Information: The online version contains supplementary material available at 10.1007/s10989-021-10279-9.