Immunoinformatics-guided design of a multi-epitope vaccine based on the structural proteins of severe acute respiratory syndrome coronavirus 2

Abstract

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), resulting in a contagious respiratory tract infection that has become a global burden since the end of 2019. Notably, fewer patients infected with SARS-CoV-2 progress from acute disease onset to death compared with the progression rate associated with two other coronaviruses, SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). Several research organizations and pharmaceutical industries have attempted to develop successful vaccine candidates for the prevention of COVID-19. However, increasing evidence indicates that the SARS-CoV-2 genome undergoes frequent mutation; thus, an adequate analysis of the viral strain remains necessary to construct effective vaccines. The current study attempted to design a multi-epitope vaccine by utilizing an approach based on the SARS-CoV-2 structural proteins. We predicted the antigenic T- and B-lymphocyte responses to four structural proteins after screening all structural proteins according to specific characteristics. The predicted epitopes were combined using suitable adjuvants and linkers, and a secondary structure profile indicated that the vaccine shared similar properties with the native protein. Importantly, the molecular docking analysis and molecular dynamics simulations revealed that the constructed vaccine possessed a high affinity for toll-like receptor 4 (TLR4). In addition, multiple descriptors were obtained from the simulation trajectories, including the root-mean-square deviation (RMSD), root-mean-square fluctuation (RMSF), solvent-accessible surface area (SASA), and radius of gyration (<i>R</i> _g), demonstrating the rigid nature and inflexibility of the vaccine and receptor molecules. In addition, codon optimization, based on <i>Escherichia coli</i> K12, was used to determine the GC content and the codon adaptation index (CAI) value, which further followed for the incorporation into the cloning vector pET28+(a). Collectively, these findings suggested that the constructed vaccine could be used to modulate the immune reaction against SARS-CoV-2.