Immunoinformatics-Driven Multiepitope Vaccine Targeting Streptococcus mutans for Dental Caries Prevention

Abstract

Abstract Streptococcus mutans is a major causative agent of dental caries and associated infections, posing significant challenges in oral healthcare. To develop an effective vaccine against S. mutans, we employed an immunoinformatics approach to identify potential vaccine candidates and design a multiepitope vaccine. The genomes of S. mutans were analyzed, and five core-proteins (PBP2X, PBP2b, MurG, ATP-F, and AGPAT) were selected as vaccine candidates based on antigenicity and conservation. Linear B-cell and T-cell epitopes were predicted from these proteins, and four B-cell epitopes and ten T-cell epitopes were chosen for vaccine construction. The multiepitope vaccine comprised 10 CTL epitopes, 5 HTL epitopes, and 5 linear B-cell epitopes linked with appropriate linkers. A 50S ribosomal L7/L12 protein was used as an adjuvant at the N-terminal. The final vaccine construct exhibited high antigenicity, solubility, and stability. The tertiary structure was modeled using AlphaFold v.2 and refined with GalaxyRefine. The refined 3D model had improved quality scores and structural stability. Molecular docking simulations revealed strong interactions between the vaccine and Toll-Like Receptors (TLRs). In silico immune simulation demonstrated the vaccine's ability to trigger both humoral and cell-mediated immune responses. The vaccine design strategy presented here provides a promising platform for developing a potential multiepitope vaccine against S. mutans, offering a novel approach to combat dental caries and associated infections. Further, experimental evaluations should be performed to validate its efficacy and safety as a potential vaccine candidate for dental health.