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基于表位的针对常见致病型疫苗的设计

Designing of an Epitope-Based Vaccine Against Common Pathotypes.

作者信息

Soltan Mohamed A, Behairy Mohammed Y, Abdelkader Mennatallah S, Albogami Sarah, Fayad Eman, Eid Refaat A, Darwish Khaled M, Elhady Sameh S, Lotfy Ahmed M, Alaa Eldeen Muhammad

机构信息

Department of Microbiology and Immunology, Faculty of Pharmacy, Sinai University, Ismailia, Egypt.

Department of Microbiology and Immunology, Faculty of Pharmacy, University of Sadat City, Sadat City, Egypt.

出版信息

Front Med (Lausanne). 2022 Mar 4;9:829467. doi: 10.3389/fmed.2022.829467. eCollection 2022.

Abstract

() is a Gram-negative bacterium that belongs to the family Enterobacteriaceae. While can stay as an innocuous resident in the digestive tract, it can cause a group of symptoms ranging from diarrhea to live threatening complications. Due to the increased rate of antibiotic resistance worldwide, the development of an effective vaccine against pathotypes is a major health priority. In this study, a reverse vaccinology approach along with immunoinformatics has been applied for the detection of potential antigens to develop an effective vaccine. Based on our screening of 5,155 proteins, we identified lipopolysaccharide assembly protein (LptD) and outer membrane protein assembly factor (BamA) as vaccine candidates for the current study. The conservancy of these proteins in the main pathotypes was assessed through BLASTp to make sure that the designed vaccine will be protective against major pathotypes. The multitope vaccine was constructed using cytotoxic T lymphocyte (CTL), helper T lymphocyte (HTL), and B cell lymphocyte (BCL) epitopes with suitable linkers and adjuvant. Following that, it was analyzed computationally where it was found to be antigenic, soluble, stable, and non-allergen. Additionally, the adopted docking study, as well as all-atom molecular dynamics simulation, illustrated the promising predicted affinity and free binding energy of this constructed vaccine against the human Toll-like receptor-4 (TLR-4) dimeric state. In this regard, wet lab studies are required to prove the efficacy of the potential vaccine construct that demonstrated promising results through computational validation.

摘要

()是一种革兰氏阴性菌,属于肠杆菌科。虽然它可以作为无害的定居菌存在于消化道中,但它也可能引发一系列症状,从腹泻到危及生命的并发症。由于全球抗生素耐药率不断上升,开发一种针对()致病型的有效疫苗是一项重大的卫生优先事项。在本研究中,一种反向疫苗学方法与免疫信息学相结合,用于检测潜在抗原以开发有效疫苗。基于对5155种蛋白质的筛选,我们确定脂多糖组装蛋白(LptD)和外膜蛋白组装因子(BamA)作为本研究的疫苗候选物。通过BLASTp评估这些蛋白质在主要()致病型中的保守性,以确保设计的疫苗对主要()致病型具有保护作用。使用细胞毒性T淋巴细胞(CTL)、辅助性T淋巴细胞(HTL)和B淋巴细胞(BCL)表位以及合适的接头和佐剂构建多表位疫苗。随后,对其进行了计算分析,发现它具有抗原性、可溶性、稳定性且无过敏原。此外,所采用的对接研究以及全原子分子动力学模拟表明,这种构建的疫苗对人 toll样受体4(TLR-4)二聚体状态具有良好的预测亲和力和自由结合能。在这方面,需要进行湿实验室研究来证明通过计算验证显示出良好结果的潜在疫苗构建体的有效性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3901/8931290/1444f9bec74b/fmed-09-829467-g0001.jpg

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