Immunoinformatics Approach for the Designing of a Novel mRNA Vaccine Candidate Against Trypanosoma brucei

IF 1.5 3区农林科学 Q4 PARASITOLOGY

Acta Parasitologica Pub Date : 2026-09-07 DOI:10.1007/s11686-026-01388-w

Monira Swapna Nil, Shupriti Khandker, Samia Sadaf, Nadia Ahmed, Salman Reja, Md. Sayfullah, Jannatul Ferdous, Suknna Saha, Abdulaziz Alamri, Mohd Shahnawaz Khan, Shakil Ahmed, Shah Wajed, Ahmad Abdullah Mahdeen, Noimul Hasan Siddiquee

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引用次数: 0

Abstract

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.

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布鲁氏锥虫新型mRNA候选疫苗设计的免疫信息学方法。

背景：布鲁氏锥虫引起非洲人类锥虫病（HAT），对个人健康造成毁灭性影响。目前，fda还没有批准用于预防HAT的疫苗。因此，利用反向疫苗学方法设计mRNA候选疫苗。方法：以布鲁氏体的变异表面糖蛋白、热休克蛋白70和空泡转运蛋白伴侣复合物为目标，预测其免疫原性、非致敏性和无毒肽。评估候选疫苗的人群覆盖率、生物物理属性、结构稳定性和精细化。分子对接、MD模拟和MM-GBSA分析评估受体结合和复合物稳定性。利用pET-28a（+）对大肠杆菌K12菌株进行密码子优化和芯片克隆。免疫模拟预测体液和细胞反应，而mRNA完整性通过MFE分析进行评估。结果：该候选疫苗实现了100%的全球人口覆盖率。生物物理属性表明脂肪性为71.23，肉汁评分为-0.719。采用稳定的验证指标（Ramachandran评分86.8%，z评分-5.26）对预测三级结构（tm评分0.65±0.13，c评分-0.50）进行细化。对接预测与TLR-2和TLR-4显著结合（能量评分-1013.5和-1002.8 kJ/mol），通过MD模拟、PCA、DCCM、MM-GBSA分析验证。密码子优化（CAI 0.9688; GC 44.70%）显示出高表达潜力，免疫模拟显示出强大的抗体和细胞介导的反应，包括B淋巴细胞、T淋巴细胞水平升高，IgM、IgG滴度升高。最后，通过MFE值预测mRNA的结构完整性。结论：该芯片设计的疫苗具有较强的结构稳定性、受体相互作用和抗布鲁氏杆菌的免疫原性。需要实验验证和体内研究来验证候选疫苗的安全性和有效性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Acta Parasitologica 医学-寄生虫学

CiteScore

3.10

自引率

6.70%

发文量

149

审稿时长

6-12 weeks

期刊介绍： Acta Parasitologica is an international journal covering the latest advances in the subject. Acta Parasitologica publishes original papers on all aspects of parasitology and host-parasite relationships, including the latest discoveries in biochemical and molecular biology of parasites, their physiology, morphology, taxonomy and ecology, as well as original research papers on immunology, pathology, and epidemiology of parasitic diseases in the context of medical, veterinary and biological sciences. The journal also publishes short research notes, invited review articles, book reviews. The journal was founded in 1953 as "Acta Parasitologica Polonica" by the Polish Parasitological Society and since 1954 has been published by W. Stefanski Institute of Parasitology of the Polish Academy of Sciences in Warsaw. Since 1992 in has appeared as Acta Parasitologica in four issues per year.