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

## TL;DR

A new mRNA vaccine targeting a protein from Streptococcus anginosus is designed to reduce gastric cancer risk by triggering strong immune responses.

## Contribution

A novel multi-epitope mRNA vaccine targeting TMPC from S. anginosus is computationally designed and validated for immunogenicity and stability.

## Key findings

- Immune simulations predicted strong humoral and cellular immune responses, including cytokine production and memory cell activation.
- Molecular docking and dynamics confirmed stable interactions between the vaccine and key immune receptors like HLA-A*02:01 and TLR2.
- The vaccine was modified as an mRNA-based version to enhance cytotoxic T-cell induction.

## Abstract

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.

Design process for messenger RNA vaccines. Candidate proteins are initially screened using immunoinformatics, after which selected epitopes are assembled into a multi‐epitope vaccine. The vaccine construct was evaluated through molecular docking, molecular dynamics simulations, and in silico immune simulations, followed by population coverage analysis and messenger RNA vaccine design.