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Computational Validation of Multi-Epitope mRNA Vaccine Targeting Streptococcus anginosus Surface Protein (TMPC) as an
Fei Zhu1,2,3, Yuying Luo1,2,3, Ziyou Zhou1,2,3
1Department of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University, Changsha, Hunan, China.
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.
Insights
A novel multi-epitope vaccine targeting Streptococcus anginosus, a bacterium linked to gastric cancer, was designed using Treponema pallidum membrane protein C (TMPC). Computational analysis predicts a strong immune response, paving the way for potential new treatments.
Area of Science:
- Microbiology
- Immunology
- Vaccine Development
Background:
- Streptococcus anginosus is associated with increased gastric cancer risk.
- Current treatments lack vaccines and face antibiotic resistance challenges.
Purpose of the Study:
- To design a multi-epitope vaccine targeting TMPC-positive streptococcal species, primarily S. anginosus.
- To evaluate the vaccine construct's immunogenicity and stability through computational methods.
Main Methods:
- Development of a TMPC-based multi-epitope vaccine construct.
- Selection of B-cell and T-cell epitopes based on binding affinity, antigenicity, and immunogenicity.
- Computational analysis including molecular docking and molecular dynamics simulations.
- Modification into a messenger RNA (mRNA) vaccine for enhanced T-cell response.
Main Results:
- The vaccine construct incorporates epitopes from nine TMPC-positive streptococcal species.
- Immune simulations predicted robust humoral and cellular immune responses.
- Molecular docking confirmed stable interactions with immune receptors (HLA and TLRs).
Conclusions:
- A TMPC-based multi-epitope vaccine candidate was computationally designed against S. anginosus.
- The vaccine shows potential for inducing significant immune responses.
- Further animal studies are required to validate immunogenicity and protective efficacy.
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