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Designing a Novel Multi-Epitope Vaccine Against Htlv-1 Related Adult T-cell Leukemia/Lymphoma: An In Silico Approach
Current Proteomics ( IF 0.5 ) Pub Date : 2021-05-31 , DOI: 10.2174/1570164617999200717232832
Elnaz Farahi 1 , Mohammad Javad Mokhtari 1 , Younes Ghasemi 2 , Navid Nezafat 2
Affiliation  

Background: Cancer is a genetic disorder in which several factors like oncoviruses are involved. Among viruses, Human T-lymphotropic virus 1 (HTLV-1) is a human oncovirus whose long-term infection leads to Adult T-Cell Leukemia/Lymphoma (ATLL).

The lack of a vaccine against HTLV-1 and limited efficacy of available treatments for ATLL due to the weakness of the immune system led us to develop novel therapeutic\prophylactic epitope vaccine, which is able to potentiate the immune system against HTLV-1.

Methods: In this research, the amino acid sequences of TAX, HBZ, gp62 and NY-ESO-1 were retrieved from the UniProt database. Afterwards, the bioinformatics analyses were performed to select the Cytotoxic T Lymphocytes (CTL) and Helper T Lymphocyte (HTL) epitopes using IEDB, RANKPEP, CTLpred and PA Complex servers. The selected epitopes, along with RS09 protein adjuvant, were connected to each other via proper amino acid linkers.

RS09 adjuvant was used as a TLR4 agonist to assure the induction of immune response. Then, the three-dimensional model of the protein vaccine was generated via Phyer2 software. In the next step, the optimization of the final structure of the protein vaccine was performed using GalaxyRefine, Galaxyloop and KOBAMIN servers.

Results: Evaluation of 3D protein vaccine with ERRAT, PROSA-web and Ramachandran plots servers showed that the vaccine possesses a high-quality structure; moreover, the vaccine was antigen and non-allergen.

Conclusion: We believe that the designed vaccine candidate can stimulate cellular and humoral immunity effectively; however, the potency of the vaccine should confirm via in vitro and in vivo immunological assays.



中文翻译:

设计一种针对 Htlv-1 相关成人 T 细胞白血病/淋巴瘤的新型多表位疫苗:一种计算机方法

背景:癌症是一种遗传性疾病,其中涉及多种因素,如癌病毒。在病毒中,人类 T 淋巴细胞病毒 1 (HTLV-1) 是一种人类癌病毒,其长期感染会导致成人 T 细胞白血病/淋巴瘤 (ATLL)。

由于免疫系统的弱点,缺乏针对 HTLV-1 的疫苗以及 ATLL 可用治疗的有效性有限,这促使我们开发了新型治疗性/预防性表位疫苗,该疫苗能够增强针对 HTLV-1 的免疫系统。

方法:本研究从UniProt数据库中检索TAX、HBZ、gp62和NY-ESO-1的氨基酸序列。然后,使用 IEDB、RANKPEP、CTLpred 和 PA Complex 服务器进行生物信息学分析以选择细胞毒性 T 淋巴细胞 (CTL) 和辅助 T 淋巴细胞 (HTL) 表位。选定的表位与 RS09 蛋白佐剂一起通过适当的氨基酸接头相互连接。

RS09 佐剂用作 TLR4 激动剂以确保诱导免疫反应。然后,通过Phyer2软件生成蛋白质疫苗的三维模型。在下一步中,使用 GalaxyRefine、Galaxyloop 和 KOBAMIN 服务器对蛋白质疫苗的最终结构进行优化。

结果:使用 ERRAT、PROSA-web 和 Ramachandran 图服务器对 3D 蛋白质疫苗的评估表明疫苗具有高质量的结构;此外,疫苗是抗原和非过敏原。

结论:我们认为设计的候选疫苗可以有效地刺激细胞和体液免疫;然而,疫苗的效力应通过体外和体内免疫学分析来确认。

更新日期:2021-05-31
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