Department of Biochemistry, School of Life Sciences, Central University of Rajasthan, Bandarsindri, Kishangarh, Ajmer, Rajasthan 305817 India.
Cellular and Molecular Neurobiology Unit, Indian Institute of Technology Jodhpur, Jodhpur, Rajasthan 342011 India.
Vaccine. 2018 Oct 8;36(42):6290-6300. doi: 10.1016/j.vaccine.2018.09.004. Epub 2018 Sep 11.
Chagas disease is a protozoan parasitic disease caused by Trypanosoma cruzi. This injurious disease spread by the circulation of the blood sucking triatomine insects and transmitted to humans. Chagas disease is endemic in Latin America and also known as American trypanosomasis. Currently, 7 million people are infected by T. cruzi infection and about 22,000 death cases were reported per year throughout the Americas. Various immunization approaches against T. cruzi infection have been examined and some of the developed vaccine showed efficacy in animal models but there is no effective and safe vaccines for humans have been developed yet. Since, the drug resistance is increasing day by day because the developed drug (nifurtimox and benznidazole) to control T. cruzi infection, failed to activate a prodrug and still no drug and vaccine have been established. To control the infection of chagas disease, here in this study we use immunoinformatics method to design multi-epitope subunit vaccine against T. cruzi infection. Moreover, on the basis of immunogenicity B and T cell epitopes were evaluated. The allergenicity, antigenicity was predicted to ensure the safety of vaccine constructs whereas, the physiochemical property showing the stable nature of final vaccine model. Further, molecular docking was performed to optimize the interaction between TLR-2 and TLR-4 (receptor) and vaccine model (ligand) complex. Molecular dynamics simulation was performed to evaluate the energy minimization; RMSD and RMSF plot which confirm the stability of TLR-2 and TLR-4 (receptor) present on immune cells and vaccine model (ligand) complex. This study needed the experimental validation for the safety and immunogenic behavior of designed vaccine protein and it may be helpful in future to control T. cruzi infection.
恰加斯病是一种由克氏锥虫引起的原生动物寄生虫病。这种有害疾病通过吸血的三锥虫传播,并传播给人类。恰加斯病在拉丁美洲流行,也被称为美洲锥虫病。目前,有 700 万人感染了克氏锥虫感染,每年在整个美洲约有 22000 人死亡。已经研究了各种针对克氏锥虫感染的免疫接种方法,一些开发的疫苗在动物模型中显示出疗效,但尚未开发出针对人类的有效和安全疫苗。由于针对克氏锥虫感染的开发药物(硝呋莫司和苯并硝唑)未能激活前药,而且仍然没有药物和疫苗,因此药物耐药性日益增加。为了控制恰加斯病的感染,在这项研究中,我们使用免疫信息学方法设计针对克氏锥虫感染的多表位亚单位疫苗。此外,根据免疫原性 B 和 T 细胞表位进行了评估。预测过敏原性和抗原性以确保疫苗构建体的安全性,而物理化学性质则显示最终疫苗模型的稳定性质。进一步进行了分子对接,以优化 TLR-2 和 TLR-4(受体)与疫苗模型(配体)复合物之间的相互作用。进行了分子动力学模拟以评估能量最小化;RMSD 和 RMSF 图证实了存在于免疫细胞上的 TLR-2 和 TLR-4(受体)和疫苗模型(配体)复合物的稳定性。这项研究需要对设计的疫苗蛋白进行安全性和免疫原性行为的实验验证,这可能有助于未来控制克氏锥虫感染。