Computational Design and Immune Profiling of a Multi-Epitope Subunit Vaccine Targeting the PAC Adhesin of Streptococcus Mutans

https://doi.org/10.5281/zenodo.18366072

Abstract

Streptococci mutans colonization and capacity to form biofilms has been major in the propagation of dental caries, which is one of the most common infectious diseases in the world. A significant pathogenic factor in bacterial adhesion to tooth enamel is the major surface adhesin PAc (antigen I/II), which is a significant therapeutic target of preventive intervention. A multi-epitope subunit vaccine against the PAc protein was constructed computationally in this study by means of an integrated workflow of immunoinformatic. The IEDB platform was used to predict antigenic, non-allergenic, and non-toxic T-cell epitopes and further filtered them based on immunogenicity, binding affinity by MHC, and conservation. The immunologically relevant linkers were used to assemble selected epitopes into a chimeric construct, which was then paired with human beta defensin as an adjuvant. ProtParam and Protein-Sol were used to analyze the physicochemical properties of the constructed vaccine, and the secondary and tertiary structures were analyzed with PSIPRED and AlphaFold and stereochemical validation was done. Molecular docking and molecular dynamics studies revealed that the construct was able to interact with immune receptors in a stable manner with good binding energies. Analysis of population coverage showed that it could be widely used globally and immune simulation showed robust humoral and cellular responses, including the formation of memory cells. In general, the computational workflow facilitates the possibility of the constructed construct as a safe and immunogenic vaccine against S. mutans, which is worth future experimental verification.