A novel in silico minigene vaccine based on CD4(+) T-helper and B-cell epitopes of EG95 isolates for vaccination against cystic echinococcosis

作者：Pourseif Mohammad M; Moghaddam Gholamali^*; Naghili Behrouz; Saeedi Nazli; Parvizpour Sepideh; Nematollahi Ahmad; Omidi Yadollah^*

来源：Computational Biology and Chemistry, 2018, 72: 150-163.

DOI：10.1016/j.compbiolchem.2017.11.008

• EG95
• T-helper epitope
• Ovar leukocyte antigen
• Docking
• B-cell epitope
• Minigene vaccine

EG95 oncospheral antigen plays a crucial role in Echinococcus granulosus pathogenicity. Considering the diversity of antigen among different EG95 isolates, it seems to be an ideal antigen for designing a universal multivalent minigene vaccine, so-called multi-epitope vaccine. This is the first in silico study to design a construct for the development of global EG95-based hydatid vaccine against E. granulosus in intermediate hosts. After antigen sequence selection, the three-dimensional structure of EG95 was modeled and multilaterally validated. The preliminary parameters for B-cell epitope prediction were implemented such as the possible transmembrane helix, signal peptide, post-translational modifications and allergenicity. The high ranked linear and conformational B-cell epitopes derived from several online web-servers (e.g., ElliPro, BepiPred v1.0, BcePred, ABCpred, SVMTrip, IEDB algorithms, SEPPA v2.0 and Discotope v2.0) were utilized for multiple sequence alignment and then for engineering the vaccine construct. T-helper based epitopes were predicted by molecular docking between the high frequent ovar class II allele (Ovar-DRB1*1202) and hexadecamer fragments of the EG95 protein. Having used the immune-informatics tools, we formulated the first EG95-based minigene vaccine based on T-helper epitope with high-binding affinity to the ovar MHC allele. This designed construct was analyzed for different physicochemical properties. It was also codon-optimized for high-level expression in Escherichia coli k12. Taken all, we propose the present in silico vaccine constructs as a promising platform for the generation of broadly protective vaccines for species and genus-specific immunization of the natural hosts of the parasite.

• 出版日期2018-2