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运用免疫信息学方法设计一种新型抗黑色素瘤多表位肽疫苗。

Designing a novel multiepitope peptide vaccine against melanoma using immunoinformatics approach.

作者信息

Yazdani Zahra, Rafiei Alireza, Irannejad Hamid, Yazdani Mohammadreza, Valadan Reza

机构信息

Department of Immunology, Molecular and Cell Biology Research Center, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.

Department of Medicinal Chemistry, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.

出版信息

J Biomol Struct Dyn. 2022 Apr;40(7):3312-3324. doi: 10.1080/07391102.2020.1846625. Epub 2020 Nov 23.

DOI:10.1080/07391102.2020.1846625
PMID:33226282
Abstract

Malignant melanoma is the most aggressive and life-threaten skin cancer. Nowadays, the prevention and treatment of melanoma are challenging areas for researchers and physicians. Therefore, we implemented an based approach to design a multi-epitope peptide vaccine for melanoma. This approach consists of immunoinformatics, molecular docking, and dynamic stimulation assessments to identify potent targets. Three most immunogenic melanoma proteins; NEYSO-1, gp-100, and MART-1were considered to predict immunodominant B and T cell epitopes. The prioritized epitopes had significant potential to induce strong humoral and cellular immunity and INF-γ responses without the possibility of allergenicity. To enhance the immunogenic properties of the vaccine, we used adjuvants HBHA, the helper epitope of PADRE, and three segments of the helper epitope from TTFrC. To design the final vaccine construct, appropriate linkers are used to join immunogenicscreened-epitopes and also the adjuvants. The physicochemical and immunological properties of the vaccine were evaluated.The designed-vaccine construct was docked to TLR4 to visualize the complex affinity and then conformational dynamics simulation was used to analyze time-dependent interaction behavior. In silico cloning demonstrated that the vaccine can be efficiently expressed in . Therefore, the designed vaccine might have the ability to induce humoral and cellular immune responses against melanoma cancer antigens. This vaccine has a high-quality structure and suitable characteristics such as high stability, solubility, and a high potential for expression in a prokaryotic system. However, these results need the experimental study to ensure the immunogenicity and safety profile of the melanoma candidate vaccine construct.

摘要

恶性黑色素瘤是最具侵袭性且危及生命的皮肤癌。如今,黑色素瘤的预防和治疗对研究人员和医生来说是具有挑战性的领域。因此,我们采用了一种基于免疫信息学、分子对接和动态刺激评估的方法来设计一种用于黑色素瘤的多表位肽疫苗,以识别有效的靶点。我们考虑了三种免疫原性最强的黑色素瘤蛋白:NEYSO-1、gp-100和MART-1,来预测免疫显性B细胞和T细胞表位。这些优先选择的表位具有显著潜力,可诱导强烈的体液免疫和细胞免疫以及INF-γ反应,且不存在致敏可能性。为增强疫苗的免疫原性特性,我们使用了佐剂HBHA、PADRE的辅助表位以及来自TTFrC辅助表位的三个片段。为设计最终的疫苗构建体,使用了合适的连接子来连接经免疫原性筛选的表位以及佐剂。对疫苗的物理化学和免疫学特性进行了评估。将设计好的疫苗构建体与TLR4进行对接以可视化复合物亲和力,然后使用构象动力学模拟来分析时间依赖性相互作用行为。计算机克隆表明该疫苗能够在……中有效表达。因此,设计的疫苗可能有能力诱导针对黑色素瘤癌抗原的体液免疫和细胞免疫反应。这种疫苗具有高质量的结构和合适特性,如高稳定性、溶解性以及在原核系统中高表达潜力。然而这些结果需要实验研究来确保黑色素瘤候选疫苗构建体的免疫原性和安全性。 (原文中“in silico cloning demonstrated that the vaccine can be efficiently expressed in.”这里“in.”后面似乎缺失了内容)

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