Acta parasitologica · 2026
Immunoinformatics Approach for the Designing of a Novel mRNA Vaccine Candidate Against Trypanosoma brucei.
СтатьяНазвание и аннотация: Перевод в очереди
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Nil Monira Swapna, Khandker Shupriti, Sadaf Samia, Ahmed Nadia, Reja Salman, Sayfullah Md, Ferdous Jannatul, Saha Suknna, Alamri Abdulaziz, Khan Mohd Shahnawaz, Ahmed Shakil, Wajed Shah, Mahdeen Ahmad Abdullah, Siddiquee Noimul Hasan
Аннотация
BACKGROUND: Trypanosoma brucei causes Human African Trypanosomiasis (HAT), which has a devastating impact on an individual's health. Currently, there is no FDA-approved vaccine for HAT prevention. Therefore, reverse vaccinology approaches were utilized to design an mRNA vaccine candidate.
METHODS: Variant surface glycoprotein, heat shock protein 70, and vacuolar transporter chaperone complex of T. brucei were targeted to predict immunogenic, non-allergenic, and non-toxic peptides. The vaccine candidate was evaluated for population coverage, biophysical attributes, structural stability, and refinement. Molecular docking, MD simulation, and MM-GBSA analyses evaluate receptor binding and complex stability. Codon optimization and in-silico cloning were conducted in Escherichia coli (strain K12) using pET-28a( +). Immune simulations predicted humoral and cellular responses, while mRNA integrity was evaluated through MFE analysis.
RESULTS: The vaccine candidate achieved 100% global population coverage. Biophysical attributes indicated aliphaticity 71.23, and GRAVY score -0.719. Predicted tertiary structure (TM-score 0.65 ± 0.13, and C-score -0.50) was refined with stable validation metrics (Ramachandran score 86.8%, and Z-score -5.26). Docking predicted significant binding with TLR-2 and TLR-4 (energy scores -1013.5 and -1002.8 kJ/mol), validated through MD simulation, PCA, DCCM, MM-GBSA analyses. Codon optimization (CAI 0.9688; GC 44.70%) indicated high expression potential, and immune simulation exhibits robust antibody and cell-mediated responses, including elevated B lymphocyte, T lymphocyte levels, and IgM, IgG titers. Finally, the structural integrity of mRNA was predicted by MFE values.
CONCLUSION: This in-silico designed vaccine demonstrated strong structural stability, receptor interactions, and immunogenic potential against T. brucei. Experimental validation and in-vivo studies are required to verify safety and efficacy of vaccine candidate.
METHODS: Variant surface glycoprotein, heat shock protein 70, and vacuolar transporter chaperone complex of T. brucei were targeted to predict immunogenic, non-allergenic, and non-toxic peptides. The vaccine candidate was evaluated for population coverage, biophysical attributes, structural stability, and refinement. Molecular docking, MD simulation, and MM-GBSA analyses evaluate receptor binding and complex stability. Codon optimization and in-silico cloning were conducted in Escherichia coli (strain K12) using pET-28a( +). Immune simulations predicted humoral and cellular responses, while mRNA integrity was evaluated through MFE analysis.
RESULTS: The vaccine candidate achieved 100% global population coverage. Biophysical attributes indicated aliphaticity 71.23, and GRAVY score -0.719. Predicted tertiary structure (TM-score 0.65 ± 0.13, and C-score -0.50) was refined with stable validation metrics (Ramachandran score 86.8%, and Z-score -5.26). Docking predicted significant binding with TLR-2 and TLR-4 (energy scores -1013.5 and -1002.8 kJ/mol), validated through MD simulation, PCA, DCCM, MM-GBSA analyses. Codon optimization (CAI 0.9688; GC 44.70%) indicated high expression potential, and immune simulation exhibits robust antibody and cell-mediated responses, including elevated B lymphocyte, T lymphocyte levels, and IgM, IgG titers. Finally, the structural integrity of mRNA was predicted by MFE values.
CONCLUSION: This in-silico designed vaccine demonstrated strong structural stability, receptor interactions, and immunogenic potential against T. brucei. Experimental validation and in-vivo studies are required to verify safety and efficacy of vaccine candidate.