Exploring dengue proteome to design an effective epitope-based vaccine against dengue virus

被引:31
|
作者
Sabetian, Soudabeh [1 ]
Nezafat, Navid [1 ,2 ]
Dorosti, Hesam [1 ,2 ]
Zarei, Mahboubeh [1 ,2 ]
Ghasemi, Younes [1 ,2 ,3 ,4 ]
机构
[1] Shiraz Univ Med Sci, Pharmaceut Sci Res Ctr, Shiraz, Iran
[2] Shiraz Univ Med Sci, Sch Pharm, Dept Pharmaceut Biotechnol, Shiraz, Iran
[3] Shiraz Univ Med Sci, Sch Adv Med Sci & Technol, Dept Med Biotechnol, Shiraz, Iran
[4] Shiraz Univ Med Sci, Biotechnol Res Ctr, Shiraz, Iran
来源
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS | 2019年 / 37卷 / 10期
关键词
Bioinformatics; epitope; dengue virus; vaccine; molecular docking; MAJOR HISTOCOMPATIBILITY COMPLEX; HEAT-LABILE ENTEROTOXINS; TOLL-LIKE RECEPTORS; PEPTIDE VACCINE; ENVELOPE GLYCOPROTEIN; PREDICTION; PROTEINS; BINDING; WEB; IMMUNOINFORMATICS;
D O I
10.1080/07391102.2018.1491890
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Dengue, a mosquito-borne disease, is caused by four known dengue serotypes. This infection causes a range of symptoms from a mild fever to a sever homorganic fever and death. It is a serious public health problem in subtropical and tropical countries. There is no specific vaccine currently available for clinical use and study on this issue is ongoing. In this study, bioinformatics approaches were used to predict antigenic, immunogenic, non-allergenic, and conserved B and T-cell epitopes as promising targets to design an effective peptide-based vaccine against dengue virus. Molecular docking analysis indicated the deep binding of the identified epitopes in the binding groove of the most popular human MHC I allele (human leukocyte antigens [HLA] A*0201). The final vaccine construct was created by conjugating the B and T-cell identified epitopes using proper linkers and adding an appropriate adjuvant at the N-terminal. The characteristics of the new subunit vaccine demonstrated that the epitope-based vaccine was antigenic, non-toxic, stable, and soluble. Other physicochemical properties of the new designed construct including isoelectric point value, aliphatic index, and grand average of hydropathicity were biologically considerable. Molecular docking of the engineered vaccine with Toll-like receptor 2 (TLR2) model revealed the hydrophobic interaction between the adjuvant and the ligand binding regions in the hydrophobic channel of TLR2. The study results indicated the high potential capability of the new multi-epitope vaccine to induce cellular and humoral immune responses against the dengue virus. Further experimental tests are required to investigate the immune protection capacity of the new vaccine construct in animal models. Communicated by Ramaswamy H. Sarma
引用
收藏
页码:2546 / 2563
页数:18
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