Designing a Self-Assembled Peptide Nano-vaccine Against Staphylococcus aureus: An In Silico Approach

Staphylococcus aureus (S. aureus) is a bacterium capable of inducing a range of human infections, varying from mild skin infections to more serious diseases like pneumonia and bloodstream infections. Different studies have focused on designing epitope vaccines against S. aureus. Nevertheless, the primary drawback of epitope vaccines is their reduced ability to stimulate an immune response. Recently, self-assembled peptide nanoparticle (SAPN) vaccines have emerged as one of the latest innovations in vaccine design. This arises from their ability to have multiple functions, act as self-adjuvants, exhibit biocompatibility, and closely resemble the size of the pathogen. Therefore, this investigation aimed to design a new SAPN vaccine to combat S. aureus infection effectively through computational approaches. Antigenic proteins ClfA, IsdB, and Hla were selected to design the SAPN vaccine. Cytotoxic T lymphocyte (CTL) epitopes from ClfA and IsdB, helper T lymphocytes (HTL) from Hla, and linear B-cell epitopes from ClfA and IsdB were chosen. Subsequently, the chosen epitopes and the oligomeric domains of the pentamer and trimmer were employed as a self-assembled framework fused with suitable linkers. Physicochemical properties, solubility, antigenicity, and allergenic potential of the designed vaccine were examined. The obtained results indicate the SAPN vaccine was antigenic, stable, and non-allergenic. Afterward, the 3D structure of the construct was initially forecasted and subsequently refined and validated to reach the best 3D model. Finally, molecular docking and molecular dynamics (MD) simulation were conducted between the SAPN vaccine and toll-like receptor 4 (TLR4). The results of molecular dynamic simulation studies demonstrated the stable interactions between the construct and TLR4. In conclusion, we devised an in silico SAPN vaccine, which is anticipated to induce robust cellular and humoral immune responses against S. aureus, making it a noteworthy prospect for subsequent in vitro and in vivo studies related to immunology.