CP91110P: A Computationally Designed Multi-Epitope Vaccine Candidate for Tuberculosis via TLR-2/4 Synergistic Immunomodulation
An Y. Ali S.L. Liu Y. Abduldayeva A. Ni R. Li Y. Zhang M. Tian Y. Jiang L. Gong W.
September 2025Multidisciplinary Digital Publishing Institute (MDPI)
Biology
2025#14Issue 9
Background: Tuberculosis (TB) remains a global health priority, with current interventions like the Bacille Calmette–Guérin (BCG) vaccine lacking efficacy against latent infection and drug-resistant strains. Novel vaccines targeting both latent and active TB are urgently needed. Objective: This study aims to design a multi-epitope vaccine (MEV) and evaluate its immunogenicity, structural stability, and interactions with toll-like receptor 2/4 (TLR-2/4) via computational biology approaches. Methods: We designed MEV using bioinformatics tools, prioritizing immunodominant epitopes from Mycobacterium tuberculosis antigens. Structural stability was optimized through disulfide engineering, and molecular docking/dynamics simulations were used to analyze interactions and conformational dynamics with TLR-2/4. Antigenicity, immunogenicity, population coverage, and immune responses were computationally assessed. Results: The MEV candidate, CP91110P, exhibited 86.18% predicted global human leukocyte antigen (HLA)-I/II coverage, high antigenicity (VaxiJen: 0.8789), and immunogenicity (IEDB: 4.40091), with favorable stability (instability index: 33.48) and solubility (0.485). Tertiary structure analysis indicated that 98.34% residues were located in favored regions. Molecular docking suggested strong TLR-2 (−1535.9 kcal/mol) and TLR-4 (−1672.5 kcal/mol) binding. Molecular dynamics simulations indicated stable TLR-2 interactions (RMSD: 6–8 Å; Rg: 38.50–39.50 Å) and flexible TLR-4 binding (RMSD: 2–6 Å; Rg: 33–36 Å). Principal component analysis, free energy landscapes, and dynamic cross-correlation matrix analyses highlighted TLR-2’s structural coherence versus TLR-4’s adaptive flexibility. Immune simulations predicted potential robust natural killer cell activation, T helper 1 polarization (interferon-gamma/interleukin-2 dominance), and elevated IgM/IgG levels. Conclusions: CP91110P is predicted to stably bind to TLR-2 and flexibly interact with TLR-4, with prediction of its high antigenicity and broad coverage across immune populations. However, this conclusion requires confirmation through experimental validation. Therefore, it may provide a promising candidate for experimental validation in the development of tuberculosis vaccines.
bioinformatics , immunogenicity , immunoinformatics , multi-epitope vaccine , tuberculosis
Text of the article Перейти на текст статьи
Beijing Key Laboratory of New Techniques of Tuberculosis Diagnosis and Treatment, Institute of Tuberculosis, Senior Department of Tuberculosis, The Eighth Medical Center of PLA General Hospital, Beijing, 100091, China
Graduate School, Hebei North University, Zhangjiakou, 075000, China
Department of Biochemistry, Abdul Wali Khan University, Mardan, 23200, Pakistan
Research Institute of Preventive Medicine named Academician E. Dalenov, Astana Medical University, Astana, 010000, Kazakhstan
Department of Immunology, College of Laboratory Medicine & Institute of Microcirculation, Hebei North University, Zhangjiakou, 075000, China
Beijing Key Laboratory of New Techniques of Tuberculosis Diagnosis and Treatment
Graduate School
Department of Biochemistry
Research Institute of Preventive Medicine named Academician E. Dalenov
Department of Immunology
10 лет помогаем публиковать статьи Международный издатель
Книга Публикация научной статьи Волощук 2026 Book Publication of a scientific article 2026