Computational Validation of Multi-Epitope mRNA Vaccine Targeting Streptococcus anginosus Surface Protein (TMPC) as an Effective Alternative Treatment to Reduce Gastric Cancer.

Streptococcus anginosus is a Gram-positive coccus that can increase gastric cancer risk through interaction with the TMPC-ANXA2-MAPK axis in gastric epithelial cells. There is currently no commercially available vaccine, and prolonged antibiotic treatment may increase drug resistance. We developed a Treponema pallidum membrane protein C (TMPC)-based multi-epitope vaccine targeting nine TMPC-positive streptococcal species dominated by S. anginosus. B-cell and T-cell epitopes were chosen based on their binding affinity, antigenicity, immunogenicity, and safety, with adjuvants and linker sequences improving construct stability and immune response. Immune simulations predicted robust humoral and cellular responses, such as cytokine production and memory cell activation. Molecular docking and molecular dynamics analysis further confirmed stable interactions between the vaccine construct and key immune receptors (HLA-A*02:01, HLA-DRB1*01:01, TLR2, and TLR4). The antigen was further modified as a messenger RNA vaccine to enhance cytotoxic T-cell induction; however, animal research is needed to confirm its immunogenicity and protective effectiveness.