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针对人类 T 淋巴细胞病毒-1 感染的多表位亚单位疫苗的组合筛选算法。

Combinatorial screening algorithm to engineer multiepitope subunit vaccine targeting human T-lymphotropic virus-1 infection.

机构信息

Department of Biochemistry, School of Life Sciences, Central University of Rajasthan, Ajmer, Rajasthan, India.

Cellular and Molecular Neurobiology Unit, Indian Institute of Technology Jodhpur, Jodhpur, Rajasthan, India.

出版信息

J Cell Physiol. 2019 Jun;234(6):8717-8726. doi: 10.1002/jcp.27531. Epub 2018 Oct 28.

Abstract

Human T-lymphotropic virus (HTLV), the first human retrovirus has been discovered which is known to cause the age-old assassinating disease HTLV-1 associated myelopathy. Cancer caused by this virus is adult T cell leukemia/lymphoma which targets 10-20 million throughout the world. The effect of this virus extends to the fact that it causes chronic disease to the spinal cord resulting in loss of sensation and further causes blood cancer. So, to overcome the complications, we designed a subunit vaccine by the assimilation of B-cell, cytotoxic T-lymphocyte , and helper T-lymphocyte epitopes. The epitopes were joined together along with adjuvant and linkers and a vaccine was fabricated which was further subjected to 3D modeling. The physiochemical properties, allergenicity, and antigenicity were evaluated. Molecular docking and dynamics were performed with the obtained 3D model against toll like receptor (TLR-3) immune receptor. Lastly, in silico cloning was performed to ensure the expression of the designed vaccine in pET28a(+) expression vector. The future prospects of the study entailed the in vitro and in vivo experimental analysis for evaluating the immune response of the designed vaccine construct.

摘要

人类 T 淋巴细胞病毒(HTLV)是第一个被发现的人类逆转录病毒,已知它会导致古老的致命疾病 HTLV-1 相关脊髓病。这种病毒引起的癌症是成人 T 细胞白血病/淋巴瘤,全世界有 1000 万至 2000 万人受到影响。这种病毒的影响还在于它会导致脊髓慢性疾病,导致感觉丧失,并进一步导致血癌。因此,为了克服这些并发症,我们通过吸收 B 细胞、细胞毒性 T 淋巴细胞和辅助 T 淋巴细胞表位,设计了一种亚单位疫苗。将这些表位与佐剂和接头一起连接起来,然后制造出一种疫苗,并进一步进行 3D 建模。评估了其理化性质、过敏性和抗原性。利用获得的 3D 模型与 Toll 样受体(TLR-3)免疫受体进行了分子对接和动力学研究。最后,进行了计算机克隆以确保设计的疫苗在 pET28a(+)表达载体中表达。该研究的未来前景包括进行体外和体内实验分析,以评估设计的疫苗构建体的免疫反应。

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