Design of a Novel Peptide-Based Vaccine Targeting Streptococcus mutans SpaP Antigen for Dental Caries Prevention.

OBJECTIVE

Dental caries is a widespread oral health issue affecting both children and adults. Streptococcus mutans (S. mutans) is a key bacterium responsible for its development. The Antigen I/II (Ag I/II; SpaP) protein of S. mutans is a promising target for a caries vaccine. Although SpaP is a validated vaccine target, conventional approaches lack epitope-level precision and rational adjuvant integration. The present study addresses this gap by computationally designing a multiepitope vaccine (MEV) targeting only the most immunogenic regions of SpaP.

METHODS

The SpaP protein sequence was retrieved from UniProtKB. Adjuvants, a TLR4 agonist from Mycobacterium tuberculosis, and the PADRE peptide were incorporated to enhance the immune response. Potential T-cell and B-cell epitopes (BCEs) were predicted using the IEDB server. They were evaluated for their ability to trigger an immune response, lack of allergenicity, and binding strength to human and mouse MHC molecules. Using appropriate linkers, selected epitopes were combined into an MEV construct. Computational analyses assessed the vaccine's properties, 3D structure, and interaction with Toll-like receptor-4 (TLR4).

RESULTS

Six MHC-I, six MHC-II, and six BCEs were indicated from SpaP, for a total of 18 epitopes selected for vaccine design. Some of these have been experimentally validated according to IEDB. This vaccine indicated potential for favorable biochemical properties, including high stability, solubility, and antigenicity. Molecular docking predicted strong vaccine-TLR4 binding affinity, with a Gibbs free energy of binding of -315.77 kcal/mol. Normal mode analysis (NMA) further suggested the stability of the vaccine-TLR4 complex and showed minimal structural changes. This study presents a novel approach to the design of SpaP-targeted vaccines.

CONCLUSION

This computationally designed MEV represents a promising candidate for experimental validation and offers a cost-effective, rational framework for developing next-generation dental caries vaccines with enhanced immunogenicity and broader protective coverage.