The Use of Reverse Vaccinology and Molecular Modeling Associated with Cell Proliferation Stimulation Approach to Select Promiscuous Epitopes from Schistosoma mansoni
The Use of Reverse Vaccinology and Molecular Modeling Associated with Cell Proliferation Stimulation Approach to Select Promiscuous Epitopes from Schistosoma mansoni
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DOI：
10.1007/s12010-016-2048-1
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发表时间：
2016-07-01
影响因子：
3
通讯作者：
Lopes, Debora D. O.
中科院分区：
文献类型：
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作者：
Oliveira, Flavio M.;Coelho, Ivan E. V.;Lopes, Debora D. O.
血吸虫病仍然是一种影响全世界数百万人的重要寄生虫病。尽管可以使用化疗，但不断发生的再感染表明需要采取其他形式的干预措施，开发疫苗是控制这种疾病的相关战略。随着基因组学和生物信息学的出现，人们提出了寻找疫苗靶点的新策略，即反向疫苗学。在这项工作中，对曼氏血吸虫膜蛋白进行了计算分析，以预测对不同人类白细胞抗原(HLA)-DRB1具有高亲和力的表位。选择10个表位，并与小鼠主要组织相容性复合体（MHC）ⅱ类分子进行三维结构优化。通过分子对接、静电势和分子体积来评价表位与小鼠MHC II类分子的相互作用。表位Sm141290和Sm050890在大多数分子建模分析中脱颖而出。细胞增殖实验评估了这些表位与小鼠MHC II分子结合并刺激CD4+ T细胞的能力，结果表明相同的表位能够显著刺激细胞增殖。这项工作显示了一种重要的肽选择策略，用于基于表位的疫苗设计，通过在体内和体外实验之前进行的硅分析实现，避免了过多的实验。
Schistosomiasis remains an important parasitic disease that affects millions of individuals worldwide. Despite the availability of chemotherapy, the occurrence of constant reinfection demonstrates the need for additional forms of intervention and the development of a vaccine represents a relevant strategy to control this disease. With the advent of genomics and bioinformatics, new strategies to search for vaccine targets have been proposed, as the reverse vaccinology. In this work, computational analyses of Schistosoma mansoni membrane proteins were performed to predict epitopes with high affinity for different human leukocyte antigen (HLA)-DRB1. Ten epitopes were selected and along with murine major histocompatibility complex (MHC) class II molecule had their three-dimensional structures optimized. Epitope interactions were evaluated against murine MHC class II molecule through molecular docking, electrostatic potential, and molecular volume. The epitope Sm141290 and Sm050890 stood out in most of the molecular modeling analyses. Cellular proliferation assay was performed to evaluate the ability of these epitopes to bind to murine MHC II molecules and stimulate CD4+ T cells showing that the same epitopes were able to significantly stimulate cell proliferation. This work showed an important strategy of peptide selection for epitope-based vaccine design, achieved by in silico analyses that can precede in vivo and in vitro experiments, avoiding excessive experimentation.