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EP9158H: An Immunoinformatics-Designed mRNA Vaccine Encoding Multi-Epitope Antigens and Dual TLR Agonists for
Mingming Zhang1,2, Syed Luqman Ali3, Yuan Tian2
1Senior Department of Tuberculosis, Chinese PLA General Hospital, Beijing 100091, China.
Bioengineering (Basel, Switzerland)
|December 30, 2025
Summary
A novel mRNA vaccine candidate, EP9158H, was designed using immunoinformatics to combat tuberculosis (TB). It integrates conserved epitopes and dual TLR agonists for enhanced immune response, offering a promising alternative to current TB vaccines.
Area of Science:
- Immunology and Vaccinology
- Computational Biology
- Infectious Diseases
Background:
- Tuberculosis (TB) poses a significant global health challenge.
- Current BCG vaccines show limited efficacy against adult pulmonary TB, necessitating new vaccine development.
- An immunoinformatics approach was employed to design a novel mRNA vaccine candidate for TB.
Purpose of the Study:
- To design a novel mRNA vaccine candidate against tuberculosis (TB) using a rational immunoinformatics approach.
- To identify and assemble optimal T-cell and B-cell epitopes with dual Toll-like receptor (TLR) agonists.
- To evaluate the computational properties, stability, and predicted immunogenicity of the designed vaccine candidate.
Main Methods:
- Selected optimal T-cell (CTL, HTL) and B-cell epitopes from 13 TB antigens.
- Assembled selected epitopes into scaffolds with TLR2 and TLR4 agonists (ESAT-6 and HBHA).
- Performed structural modeling, molecular dynamics, docking, immune simulation, RNAfold, and conservation analysis for the lead candidate EP9158H.
Main Results:
- Identified EP9158H as the optimal candidate, incorporating 15 CTL, 9 HTL, and 8 B-cell epitopes with dual TLR2/4 agonism.
- Demonstrated high epitope conservation (>81%) across Mycobacterium tuberculosis complex (MTBC) lineages.
- Showcased favorable predicted properties including high solubility, broad population coverage, optimal docking scores, structural stability, strong Th1-biased immune response, and stable mRNA secondary structure.
Conclusions:
- EP9158H represents a promising novel mRNA vaccine candidate for TB, integrating broad epitope coverage and dual innate immune activation.
- The vaccine design leverages mRNA technology for enhanced CTL induction and offers superior strain coverage compared to single-antigen vaccines.
- Computational validation supports the potential of EP9158H, warranting further experimental investigation and validation.
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