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设计一种多表位亚单位疫苗,以免疫保护抵抗利什曼原虫寄生虫。

Design of a multi-epitope subunit vaccine for immune-protection against Leishmania parasite.

机构信息

School of Biochemical Engineering, Indian Institute of Technology (BHU) Varanasi , Varanasi, India.

Molecular and Structural Biophysics Laboratory, Department of Biochemistry, North-EasternHill University , Shillong, India.

出版信息

Pathog Glob Health. 2020 Dec;114(8):471-481. doi: 10.1080/20477724.2020.1842976. Epub 2020 Nov 8.

Abstract

Visceral Leishmaniasis (VL) is an insect-borne neglected disease caused by the protozoan parasite . In the absence of a commercial vaccine against VL, chemotherapy is currently the only option used for the treatment of VL. Vaccination has been considered as the most effective and powerful tool for complete eradication and control of infectious diseases. In this study, we aimed to design a peptide-based vaccine against using immuno-bioinformatic tools. We identified 6 HTL, 18 CTL, and 25 B-cell epitopes from three hypothetical membrane proteins of . All these epitopes were used to make a vaccine construct along with linkers. An adjuvant was also added at the N-terminal to enhance its immunogenicity. After that, we checked the quality of this vaccine construct and found that it is nontoxic, nonallergic, and thermally stable. A 3D structure of the vaccine construct was also generated by homology modeling to evaluate its interaction with innate immune receptors (TLR). Molecular docking was performed, which confirmed its binding with a toll-like receptor-2 (TLR-2). The stability of vaccine-TLR-2 complex and underlying interactions were evaluated using molecular dynamic simulation. Lastly, we carried out cloning to check the expression of the final designed vaccine. The designed vaccine construct needs further experimental and clinical investigations to develop it as a safe and effective vaccine against VL infection.

摘要

内脏利什曼病(VL)是一种由原生动物寄生虫引起的虫媒传播的被忽视疾病。在没有针对 VL 的商业疫苗的情况下,化学疗法目前是治疗 VL 的唯一选择。疫苗接种被认为是彻底消除和控制传染病的最有效和最有力的工具。在这项研究中,我们旨在使用免疫生物信息学工具设计针对 的肽疫苗。我们从 的三个假设的膜蛋白中鉴定了 6 个 HTL、18 个 CTL 和 25 个 B 细胞表位。所有这些表位都与接头一起用于制造疫苗构建体。还在 N 端添加了佐剂以增强其免疫原性。之后,我们检查了这种疫苗构建体的质量,发现它是无毒、无过敏且热稳定的。还通过同源建模生成了疫苗构建体的 3D 结构,以评估其与先天免疫受体(TLR)的相互作用。进行了分子对接,证实了它与 Toll 样受体-2(TLR-2)的结合。使用分子动力学模拟评估了疫苗-TLR-2 复合物的稳定性和潜在相互作用。最后,我们进行了 克隆以检查最终设计的疫苗的表达。需要进一步的实验和临床研究来开发针对 VL 感染的安全有效的疫苗。

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